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Sample records for chronically hyperammonemic rats

  1. Cerebral ammonia metabolism in hyperammonemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, A J; Mora, S N; Cruz, N F; Gelbard, A S

    1985-06-01

    The short-term metabolic fate of blood-borne (/sup 13/N)ammonia was determined in the brains of chronically (8- or 14-week portacaval-shunted rats) or acutely (urease-treated) hyperammonemic rats. Using a freeze-blowing technique it was shown that the overwhelming route for metabolism of blood-borne (/sup 13/N)ammonia in normal, chronically hyperammonemic and acutely hyperammonemic rat brain was incorporation into glutamine (amide). However, the rate of turnover of (/sup 13/N)ammonia to L-(amide-/sup 13/N)glutamine was slower in the hyperammonemic rat brain than in the normal rat brain. The activities of several enzymes involved in cerebral ammonia and glutamate metabolism were also measured in the brains of 14-week portacaval-shunted rats. The rat brain appears to have little capacity to adapt to chronic hyperammonemia because there were no differences in activity compared with those of weight-matched controls for the following brain enzymes involved in glutamate/ammonia metabolism: glutamine synthetase, glutamate dehydrogenase, aspartate aminotransferase, glutamine transaminase, glutaminase, and glutamate decarboxylase. The present findings are discussed in the context of the known deleterious effects on the CNS of high ammonia levels in a variety of diseases.

  2. Antioxidant Potential of Momordica Charantia in Ammonium Chloride-Induced Hyperammonemic Rats

    Directory of Open Access Journals (Sweden)

    A. Justin Thenmozhi

    2011-01-01

    Full Text Available The present study was aimed to investigate the antioxidant potential of Momordica charantia fruit extract (MCE in ammonium chloride-induced (AC hyperammonemic rats. Experimental hyperammonemia was induced in adult male Wistar rats (180–200 g by intraperitoneal injections of ammonium chloride (100 mg kg−1 body weight thrice a week. The effect of oral administration (thrice a week for 8 consecutive weeks of MCE (300 mg kg−1 body weight on blood ammonia, plasma urea, serum liver marker enzymes and oxidative stress biomarkers in normal and experimental animals was analyzed. Hyperammonemic rats showed a significant increase in the activities of thiobarbituric acid reactive substances, hydroperoxides and liver markers (alanine transaminase, aspartate transaminase and alkaline phosphatase, and the levels of glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione were decreased in the liver and brain tissues. Treatment with MCE normalized the above-mentioned changes in hyperammonemic rats by reversing the oxidant-antioxidant imbalance during AC-induced hyperammonemia, and offered protection against hyperammonemia. Our results indicate that MCE exerting the antioxidant potentials and maintaining the cellular integrity of the liver tissue could offer protection against AC-induced hyperammonemia. However, the exact underlying mechanism is yet to be investigated, and examination of the efficacy of the active constituents of the M. charantia on hyperammonemia is desirable.

  3. Urea cycle pathway targeted therapeutic action of naringin against ammonium chloride induced hyperammonemic rats.

    Science.gov (United States)

    Ramakrishnan, Arumugam; Vijayakumar, Natesan

    2017-10-01

    Ammonia is a well-known neurotoxin that causes liver disease and urea cycle disorder. Excessive ammonia content in the blood leads to hyperammonemic condition and affects both excitatory and inhibitory neurotransmission including brain edema and coma. Naringin, a plant bioflavonoid present in various citrus fruits and mainly extracted from the grape fruit. This study was designed to assess the protective effect of naringin on ammonium chloride (NH 4 Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitoneal injections (i.p) of NH 4 Cl (100mg/kg body weight (b.w.)) thrice a week for 8 consecutive weeks. Hyperammonemic rats were treated with naringin (80mg/kg b.w.) via oral gavage. Naringin administration significantly augmented the level of blood ammonia and plasma urea. Naringin also upregulate the expression of urea cycle enzymes such as carbamoyl phosphate synthase I (CPS I) and ornithine transcarbamylase (OTC), arininosuccinate synthase (ASS), argininosuccinate lyase (ASL) and arginase I (ARG) and metabotropic glutamate receptors (mGluRs) such as mGluRs I and mGluRs V and down regulate the expression of inflammatory markers like tumor necrosis factor (TNF-α), nuclear factor kappa B (NF-kB), Interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS). In addition, to this, the protective effect of naringin was also revealed through the immunohistochemical changes in tissues. Thus our present study result suggest that naringin modulates the expression of proteins involved in urea cycle pathway and suppresses the expression of inflammatory markers and acts as a potential agent to treat condition in rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

    Science.gov (United States)

    Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

    2012-06-01

    Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

  5. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.

    Science.gov (United States)

    Cichoż-Lach, Halina; Michalak, Agata

    2013-01-07

    Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses.

  6. Protective effect of morin on lipid peroxidation and lipid profile in ammonium chloride-induced hyperammonemic rats

    OpenAIRE

    S Subash; P Subramanian

    2012-01-01

    Objective: To evaluated the protective effects of morin (3, 5, 7, 2', 4'-pentahydroxyflavone) on lipid peroxidation and lipid levels during ammonium chloride (AC) induced hyperammonemia in experimental rats. Methods: Thirty two male albino Wistar rats, which are weighing between 180-200 g were used for the study. The hyperammonemia was induced by administration of 100 mg/kg body weight (i.p. ) thrice in a week of AC for 8 weeks. Rats were treated with morin at dose (30 mg/kg bo...

  7. Protective effect of morin on lipid peroxidation and lipid profile in ammonium chloride-induced hyperammonemic rats

    Directory of Open Access Journals (Sweden)

    S Subash

    2012-04-01

    Full Text Available Objective: To evaluated the protective effects of morin (3, 5, 7, 2', 4'-pentahydroxyflavone on lipid peroxidation and lipid levels during ammonium chloride (AC induced hyperammonemia in experimental rats. Methods: Thirty two male albino Wistar rats, which are weighing between 180-200 g were used for the study. The hyperammonemia was induced by administration of 100 mg/kg body weight (i.p. thrice in a week of AC for 8 weeks. Rats were treated with morin at dose (30 mg/kg body weight via intragastric intubations together with AC. At the end of experimental duration, blood ammonia, plasma urea, lipid peroxidation indices [thiobarbituric acid reactive substances, hydroperoxides and lipid levels (cholesterol, triglycerides, free fatty acids and phospholipids] in serum and tissues were analysed to evaluate the antiperoxidative and antilipidemic effects of morin. Results: Ammonia, urea, lipid peroxidative indices and lipid levels were significantly increased in AC administered group. Morin treatment resulted in positive modulation of ammonia, urea, lipid peroxidative indices and lipid levels. Morin administration to normal rats did not exhibit any significant changes in any of the parameters studied. Conclusions: It can be concluded that the beneficial effect of morin on ammonia, urea, lipid peroxidative indices and lipid levels could be due to its antioxidant property.

  8. Acute hyperammonemic encephalopathy with features on diffusion-weighted images: Report of two cases

    International Nuclear Information System (INIS)

    Kim, Ja Young; Yu, In Kyu

    2015-01-01

    Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

  9. Acute hyperammonemic encephalopathy with features on diffusion-weighted images: Report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ja Young; Yu, In Kyu [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)

    2015-02-15

    Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

  10. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy

    OpenAIRE

    Cichoż-Lach, Halina; Michalak, Agata

    2013-01-01

    Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause ne...

  11. Hyperammonemic Coma—Barking Up the Wrong Tree

    Science.gov (United States)

    Kruzel-Davila, Eti; Dori, Guy; Baron, Elzbieta; Bitterman, Haim

    2007-01-01

    Hepatic encephalopathy and myxedema coma share clinical features: coma, ascites, anemia, impaired liver functions, and a “metabolic” electroencephalogram (EEG). Hyperammonemia, a hallmark of hepatic encephalopathy, has also been described in hypothyroidism. Differentiation between the 2 conditions, recognition of their possible coexistence, and the consequent therapeutic implications are of utmost importance. We describe a case of an 82-year-old woman with a history of mild chronic liver disease who presented with hyperammonemic coma unresponsive to conventional therapy. Further investigation disclosed severe hypothyroidism. Thyroid hormone replacement resulted in gain of consciousness and normalization of hyperammonemia. In patients with an elevated ammonia level, altered mental status, and liver disease, who do not have a clear inciting event for liver disease decompensation, overwhelming evidence of hepatic decompensation, or who do not respond to appropriate therapy for hepatic encephalopathy, hypothyroidism should be considered and evaluated. PMID:17372808

  12. A Case of Valproate Induced Hyperammonemic Encephalopathy

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    Surjit Tarafdar

    2011-01-01

    Full Text Available A 36-years-old man on phenytoin, levetiracetam, and sodium valproate presented with acute confusion. Routine investigations including serum valproate and phenytoin concentration were normal. His serum ammonia concentration was raised. His valproate was held and 2 days later he recovered with concordant normalisation of serum ammonia concentration. Urea acid cycle disorder was ruled out, and a diagnosis of valproate induced hyperammonemic encephalopathy (VHE was made. Asymptomatic hyperammonemia occurs in 15–50% of valproate-treated patients, and while the true incidence of VHE is not known, it is a recognized complication of sodium valproate treatment. VHE typically presents acutely with impaired consciousness, lethargy, and vomiting. Valproate concentrations may be in the therapeutic range, and liver function tests are typically “normal.” Treatment for VHE consists of ceasing valproate and providing supportive care. Some have advocated carnitine replacement.

  13. Induced Chronic Prostatitis in Rats

    African Journals Online (AJOL)

    Similarly, compared with reference group (176.1 ± 12.1 pg/ml), IL-1β level of prostate tissues of high-dose PCS ..... Fig 1: Effect of PCS extract on the histomorphology of prostate tissues in rats. ... involved with cellular recruitment, fever, acute.

  14. Damage of hippocampal neurons in rats with chronic alcoholism

    OpenAIRE

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

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons i...

  15. Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder.

    Science.gov (United States)

    Lee, Brendan; Diaz, George A; Rhead, William; Lichter-Konecki, Uta; Feigenbaum, Annette; Berry, Susan A; Le Mons, Cindy; Bartley, James A; Longo, Nicola; Nagamani, Sandesh C; Berquist, William; Gallagher, Renata; Bartholomew, Dennis; Harding, Cary O; Korson, Mark S; McCandless, Shawn E; Smith, Wendy; Cederbaum, Stephen; Wong, Derek; Merritt, J Lawrence; Schulze, Andreas; Vockley, Jerry; Vockley, Gerard; Kronn, David; Zori, Roberto; Summar, Marshall; Milikien, Douglas A; Marino, Miguel; Coakley, Dion F; Mokhtarani, Masoud; Scharschmidt, Bruce F

    2015-07-01

    The aim of this study was to examine predictors of ammonia exposure and hyperammonemic crises in patients with urea cycle disorders. The relationships between fasting ammonia, daily ammonia exposure, and hyperammonemic crises were analyzed in >100 patients with urea cycle disorders. Fasting ammonia correlated strongly with daily ammonia exposure (r = 0.764; P 200% (P urea cycle disorder subtype, dietary protein intake, or blood urea nitrogen. Fasting glutamine correlated weakly with daily ammonia exposure assessed as 24-hour area under the curve and was not a significant predictor of hyperammonemic crisis. Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of hyperammonemic crises, suggesting that patients with urea cycle disorder may benefit from tight ammonia control.

  16. Damage of hippocampal neurons in rats with chronic alcoholism.

    Science.gov (United States)

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

    2014-09-01

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

  17. Enhanced Gamma Oscillatory Activity in Rats with Chronic Inflammatory Pain

    OpenAIRE

    Wang, Jing; Wang, Jing; Xing, Guo-Gang; Li, Xiaoli; Wan, You

    2016-01-01

    It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic infla...

  18. Severe valproate induced hyperammonemic encephalopathy successfully managed with peritoneal dialysis.

    Science.gov (United States)

    Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S

    2014-07-01

    Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.

  19. Brain MRS glutamine as a biomarker to guide therapy of hyperammonemic coma.

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    O'Donnell-Luria, Anne H; Lin, Alexander P; Merugumala, Sai K; Rohr, Frances; Waisbren, Susan E; Lynch, Rebecca; Tchekmedyian, Vatche; Goldberg, Aaron D; Bellinger, Andrew; McFaline-Figueroa, J Ricardo; Simon, Tracey; Gershanik, Esteban F; Levy, Bruce D; Cohen, David E; Samuels, Martin A; Berry, Gerard T; Frank, Natasha Y

    2017-05-01

    Acute idiopathic hyperammonemia in an adult patient is a life-threatening condition often resulting in a rapid progression to irreversible cerebral edema and death. While ammonia-scavenging therapies lower blood ammonia levels, in comparison, clearance of waste nitrogen from the brain may be delayed. Therefore, we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine levels, the major reservoir of ammonia, in a gastric bypass patient with hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia-scavenging agents, sodium phenylacetate and sodium benzoate. Improvement in mental status mirrored brain glutamine levels, as coma persisted for 48h after plasma ammonia normalized. We hypothesize that the slower clearance for brain glutamine levels accounts for the delay in improvement following initiation of treatment in cases of chronic hyperammonemia. We propose MRS to monitor brain glutamine as a noninvasive approach to be utilized for diagnostic and therapeutic monitoring purposes in adult patients presenting with idiopathic hyperammonemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Chronic Tea Consumption Lowers Blood Pressure in Rats: Some ...

    African Journals Online (AJOL)

    Chronic Tea Consumption Lowers Blood Pressure in Rats: Some Associated Mechanisms. ... Nigerian Journal of Health and Biomedical Sciences ... In experiment 5, group 9 (kept on NF and indomethacin solution) also had similar BP as group 10 (kept on ... KEY WORDS: Blood pressure (BP), heart rate (HR), rats, tea.

  1. Fatal Hyperammonemic Brain Injury from Valproic Acid Exposure

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    Danny Bega

    2012-12-01

    Full Text Available Background: Hyperammonemia is known to cause neuronal injury, and can result from valproic acid exposure. Prompt reduction of elevated ammonia levels may prevent permanent neurological injury. We report a case of fatal hyperammonemic brain injury in a woman exposed to valproic acid. Case: A 38-year-old woman with schizoaffective disorder and recent increase in valproic acid dosage presented with somnolence and confusion and rapidly progressed to obtundation. Brain MRI showed diffuse bilateral restricted diffusion in nearly the entire cerebral cortex. She had normal liver function tests but serum ammonia level was severely elevated at 288 µmol/l. Genetic testing showed no mutation in urea cycle enzymes. Despite successful elimination of ammonia with hemodialysis she developed fatal cerebral edema. Conclusion: Cerebral edema secondary to hyperammonemia is potentially reversible if recognized early. Ammonia excretion can be facilitated by initiation of hemodialysis and administration of scavenging agents (sodium phenylacetate and sodium benzoate. Severe hyperammonemia can result from valproic acid exposure even in the absence of hepatotoxicity or inborn errors of metabolism. It is important to check serum ammonia in any patient with encephalopathy who has had recent valproic acid exposure.

  2. Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure

    Science.gov (United States)

    Gurbuz, Nilgun; Kol, Arif; Ipekci, Tumay; Ates, Erhan; Baykal, Asli; Usta, Mustafa F

    2015-01-01

    The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P chronic sildenafil administration on erectile function in CRF-induced rats. PMID:25652632

  3. GLUTAMINE AND HYPERAMMONEMIC CRISES IN PATIENTS WITH UREA CYCLE DISORDERS

    Science.gov (United States)

    Lee, B.; Diaz, G.A.; Rhead, W.; Lichter-Konecki, U.; Feigenbaum, A.; Berry, S.A.; Le Mons, C.; Bartley, J.; Longo, N.; Nagamani, S.C.; Berquist, W.; Gallagher, R.C.; Harding, C.O.; McCandless, S.E.; Smith, W.; Schulze, A.; Marino, M.; Rowell, R.; Coakley, D.F.; Mokhtarani, M.; Scharschmidt, B.F.

    2016-01-01

    Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. Methods The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. Results The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8–29%) as compared with 56% (28%–154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >900 µmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2] µmol/L) than patients with baseline glutamine ≤900 µmol/L (26.6 [18.0] µmol/L). Glutamine values >900 µmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR]=1.98; p=0.173). However, glutamine lost predictive significance (OR=1.47; p=0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥ 1.0 upper limit of normal (ULN) was highly statistically significant (OR=4.96; p=0.013). There was no significant effect of glutamine >900 µmol/L on time to first HAC crisis (hazard ratio [HR]=1.14; p=0.813), but there was a significant effect of baseline ammonia ≥ 1.0 ULN (HR=4.62; p=0.0011). Conclusions The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels. PMID:26586473

  4. Acute hyperammonemic encephalopathy after fluoropyrimidine-based chemotherapy: A case series and review of the literature.

    Science.gov (United States)

    Mitani, Seiichiro; Kadowaki, Shigenori; Komori, Azusa; Sugiyama, Keiji; Narita, Yukiya; Taniguchi, Hiroya; Ura, Takashi; Ando, Masashi; Sato, Yozo; Yamaura, Hidekazu; Inaba, Yoshitaka; Ishihara, Makoto; Tanaka, Tsutomu; Tajika, Masahiro; Muro, Kei

    2017-06-01

    Acute hyperammonemic encephalopathy induced by fluoropyrimidines (FPs) is a rare complication. Its pathophysiology remains unclear, especially given the currently used regimens, including intermediate-doses of 5-fluorouracil (5-FU) or oral FP agents. We aimed to characterize the clinical manifestations in cancer patients who developed hyperammonemic encephalopathy after receiving FP-based chemotherapy.We retrospectively reviewed 1786 patients with gastrointestinal or primary-unknown cancer who received FP-based regimens between 2007 and 2012. Eleven patients (0.6%) developed acute hyperammonemic encephalopathy. The incidence according to the administered anticancer drugs were as follows: 5-FU (8 of 1176, 0.7%), S-1 (1 of 679, 0.1%), capecitabine (2 of 225, 0.9%), and tegafur-uracil (UFT) (0 of 39, 0%). Ten patients (90.9%) had at least 1 aggravating factor, including infection, dehydration, constipation, renal dysfunction, and muscle loss. All the 10 patients met the definition of sarcopenia. Median time to the onset of hyperammonemic encephalopathy in the cycle was 3 days (range: 2-21). Three patients (27.3%) developed encephalopathy during the first cycle of the regimen and the remaining 8 patients during the second or more cycles. Seven patients (63.6%) had received at least 1 other FP-containing regimen before without episodes of encephalopathy.All patients recovered soon after immediate discontinuation of chemotherapy and supportive therapies, such as hydration, infusion of branched-chain amino acids, and oral lactulose intake, with a median time to recovery of 2 days (range: encephalopathy due to S-1 monotherapy, received modified FOLFOX-6 therapy without encephalopathy later.FP-associated acute hyperammonemic encephalopathy is extremely rare, but a possible event at any time and even during the administration of oral FP agents. Particular attention is warranted when giving FP-based therapy for patients with aggravating factors, such as sarcopenia. This

  5. Fetal contamination with cadmium following chronic exposure of rat ...

    African Journals Online (AJOL)

    Fetal contamination with cadmium following chronic exposure of rat dams during gestation. ... African Journal of Applied Zoology and Environmental Biology ... It was concluded that cadmium, contrary to previous reports, can pass through the placenta in appreciable quantity to contaminate the fetus to possibly cause fetal ...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes...

  7. Monitoring of gluconeogenesis in rats following chronic irradiation

    International Nuclear Information System (INIS)

    Paulikova, E.; Sedlakova, A.; Praslicka, M.

    1984-01-01

    A dose dependent cumulation of liver glycogen with the maximum on the day 120 was observed as was an increased incorporation of 14 C-alanine in liver glycogen (statistically nonsignificant changes). The contribution of 14 C-acetate to gluconeogenesis was negligible. The results showed increased gluconeogenesis in rats following chronic gamma irradiation with small daily dose rates (0.0957 Gy)

  8. Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Magata, Yasuhiro; Kitano, Haruhiro; Shiozaki, Toshiki; Iida, Yasuhiko; Nishizawa, Sadahiko; Saji, Hideo; Konishi, Junji

    2000-01-01

    The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3 H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125 I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions

  9. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  10. Variety of immune responses to chronic stress in rats male

    Directory of Open Access Journals (Sweden)

    Іlona S Polovynko

    2016-12-01

    Full Text Available Background. Previously we have been carry out integrated quantitative estimation of neuroendocrine and immune responses to chronic restraint stress in male rats. Revealed that the value of canonical discriminant roots rats subjected to chronic stress different not only on the values of intact animals (by definition, but also among themselves. So we set a goal retrospectively divided stressed rats into three homogeneous groups. Material and methods. The experiment is at 50 white male rats. Of these 10 animals not subjected to any influences and 40 within 7 days subjected to moderate stress by daily 30-minute immobilization. The day after the completion of stressing in portion of the blood immunological parameters were determined by tests I and II levels of WHO. The spleen and thymus did smears for counting spleno- and thymocytograms. Results. The method of cluster analysis (k-means clustering formed three groups-clusters. For further analysis selected 18 parameters that members of each cluster differing minimum and maximum are different from members of other clusters (η2=0,73÷0,15; F=49,0÷3,26; p=10-6÷0,05. We stated that in 16 rats from cluster III the deviation 16 parameters in either side of the average norm almost identical and are in an acceptable range of ±0,5σ. Thus, the immune status of 40% of the rats subjected to moderate chronic stress was resistant to its factors. For the immune status of the 15 (37,5% rats cluster II typical moderate inhibition microphage, killer and T-cellular links in combination with a strong activation macrophage link. Poststressory changes in immunity in 9 rats (22,5% from cluster I differ from those in cluster II both qualitatively and quantitatively. In particular, the rats in this cluster were found no deviations from the norm or reaction blast transformation T-cells nor NK-lymphocytes levels. However, other parameters of T-link and microhage link suppressed more and settings macrophage link appeared

  11. Brain perfusion in acute and chronic hyperglycemia in rats

    International Nuclear Information System (INIS)

    Kikano, G.E.; LaManna, J.C.; Harik, S.I.

    1989-01-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose

  12. Chronic intrathecal cannulation enhances nociceptive responses in rats

    Directory of Open Access Journals (Sweden)

    Almeida F.R.C.

    2000-01-01

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

  13. Water metabolism in rats subjected to chronic alcohol administration

    DEFF Research Database (Denmark)

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

    2004-01-01

    AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion ...... the body as hidden water loss increases after alcohol consumption by up to 25-26% over control values.......AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion...... and certain renal functions in rats during a period of 12 months. ANIMALS AND STUDY DESIGN: Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats of each group during 7 days, at monthly intervals...

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

    Directory of Open Access Journals (Sweden)

    Kewir D Nyuyki

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

  15. Study of the biochemical indicators of chronic irradiation in rats.

    Science.gov (United States)

    Szabo, L D; Benko, A B; Gyenge, L; Predmerszky, T

    1976-01-01

    Daily urinary excretion of pseudouridine, creatinine and creatine of chronically irradiated Wistar rats was estimated. The irradiation conditions were: 60Co gamma source, dose-rate 10 rad/day, total dose 200, 400 and 600 rad. Control groups were kept under similar conditions. Urine samples were taken three times after the end of the irradiation period. It was found that: (1) pseudouridine excretion seems more suitable for indicating radiation injury than the creatine/creatinine ratio in chronic irradiation in rats; (ii) there are significant changes in dose dependence of pseudouridine excretion in the post-irradiation period; (iii) a new method for pseudouridine estimation gives closely similar data to those of earlier investigations.

  16. Valproic acid-induced hyperammonemic encephalopathy - a potentially fatal adverse drug reaction.

    Science.gov (United States)

    Sousa, Carla

    2013-12-01

    A patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid. A patient with an early diagnosed epilepsy, treated with valproic acid, experienced an altered mental state after 10 days of treatment. Valproic acid serum levels were within limits, hepatic function tests were normal but ammonia levels were above the normal range. Valproic acid was stopped and the hyperammonemic encephalopathy was treated with lactulose 15 ml twice daily, metronidazole 250 mg four times daily and L-carnitine 1 g twice daily. Monitoring liver function and ammonia levels should be recommended in patients taking valproic acid. The constraints of the pharmaceutical market had to be taken into consideration and limited the pharmacological options for this patient's treatment. Idiosyncratic symptomatic hyperammonemic encephalopathy is completely reversible, but can induce coma and even death, if not timely detected. Clinical pharmacists can help detecting adverse drug reactions and provide evidence based information for the treatment.

  17. Monitoring of gluconeogenesis in rats following chronic irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Paulikova, E.; Sedlakova, A.; Praslicka, M. (Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie)

    1984-01-01

    A dose dependent cumulation of liver glycogen with the maximum on the day 120 was observed as was an increased incorporation of /sup 14/C-alanine in liver glycogen (statistically nonsignificant changes). The contribution of /sup 14/C-acetate to gluconeogenesis was negligible. The results showed increased gluconeogenesis in rats following chronic gamma irradiation with small daily dose rates (0.0957 Gy).

  18. Effects of chronic treatment with 7-nitroindazole in hyperthyroid rats.

    Science.gov (United States)

    Wangensteen, Rosemary; Rodríguez-Gómez, Isabel; Moreno, Juan Manuel; Alvarez-Guerra, Miriam; Osuna, Antonio; Vargas, Félix

    2006-11-01

    This study analyzed the contribution of neuronal nitric oxide synthase (nNOS) to the hemodynamic manifestations of hyperthyroidism. The effects on hyperthyroid rats of the chronic administration of 7-nitroindazole (7-NI), an inhibitor of nNOS, were studied. Six groups of male Wistar rats were used: control, 7-NI (30 mg.kg-1.day-1 by gavage), T(4)50, T(4)75 (50 or 75 microg thyroxine.rat-1.day-1, respectively), T(4)50+7-NI, and T(4)75+7-NI. All treatments were maintained for 4 wk. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, pulse pressure (PP), and HR were measured in conscious rats, and morphological, metabolic, plasma, and renal variables were determined. Expression of nNOS in the hypothalamus of T(4)75 and control rats was analyzed by Western blot analysis. The response of mean arterial pressure (MAP) to pentolinium (10 mg/kg iv) was used to evaluate the sympathetic contribution to BP in T(4)75 and T(4)75+7-NI rats. T(4) produced an increased hypothalamic nNOS expression and dose-related increases in blood pressure (BP), HR, and PP vs. control rats. 7-NI did not modify BP or any other hemodynamic variable in normal rats. However, 7-NI produced a marked reduction in BP, HR, PP, and food and water intake in both hyperthyroid groups and improved creatinine clearance in the T(4)75 group. Pentolinium produced a greater MAP decrease in the T(4)75+7-NI than in the T(4)75 group. In conclusion, administration of 7-NI attenuates the hemodynamic and metabolic manifestations of hyperthyroidism, suggesting that nNOS contributes to the hyperdynamic circulation of this endocrine disease by modulating sympathetic activity.

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

    Science.gov (United States)

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M

    2014-09-01

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

  20. Energy expenditures & physical activity in rats with chronic suboptimal nutrition.

    Science.gov (United States)

    Rising, Russell; Lifshitz, Fima

    2006-01-31

    Sub-optimally nourished rats show reduced growth, biochemical and physiological changes. However, no one has assessed metabolic rate adaptations in rats subjected to chronic suboptimal nutrition (CSN). In this study energy expenditure (EE; kcal/100 g body weight) and physical activity (PA; oscillations in weight/min/kg body weight) were assessed in rats subjected to three levels of CSN. Body weight gain was diminished (76.7 +/- 12.0 and 61.6 +/- 11.0 g) in rats fed 70 and 60% of the ad-libitum fed controls which gained more weight (148.5 +/- 32.3 g). The rats fed 80% gained weight similarly to controls (136.3 +/- 10.5 g). Percent Fat-free body mass was reduced (143.8 +/- 8.7 and 142.0 +/- 7.6 g) in rats fed 70 and 60% of ad-libitum, but not in those fed 80% (200.8 +/- 17.5 g) as compared with controls (201.6 +/- 33.4 g). Body fat (g) decreased in rats fed 80% (19.7 +/- 5.3), 70% (15.3 +/- 3.5) and 60% (9.6 +/- 2.7) of ad-libitum in comparison to controls (26.0 +/- 6.7). EE and PA were also altered by CSN. The control rats increased their EE and PA during the dark periods by 1.4 +/- 0.8 and 1.7 +/- 1.1 respectively, as compared with light the period; whereas CSN rats fed 80 and 70% of ad-libitum energy intake had reduced EE and PA during the dark periods as compared with the light period EE(7.5 +/- 1.4 and 7.8 +/- 0.6 vs. 9.0 +/- 1.2 and 9.7 +/- 0.8; p vs. 4.1 +/- 0.9 and 2.4 +/- 0.4; p vs. 0.95 +/- 0.03 and 0.91 +/- 0.05 p light (7.1 +/- 1.4) and dark period (6.2 +/- 1.0) EE and PA (3.4 +/- 0.9 and 2.5 +/- 0.5 respectively) were reduced in rats fed 60% of ad-libitum energy intake. CSN rats adapt to mild energy restriction by reducing body fat, EE and PA mainly during the dark period while growth proceeds and lean body mass is preserved. At higher levels of energy restrictions there is decreased growth, body fat and lean mass. Moreover EE and PA are also reduced during both light and dark periods.

  1. Energy expenditures & physical activity in rats with chronic suboptimal nutrition

    Directory of Open Access Journals (Sweden)

    Lifshitz Fima

    2006-01-01

    Full Text Available Abstract Background Sub-optimally nourished rats show reduced growth, biochemical and physiological changes. However, no one has assessed metabolic rate adaptations in rats subjected to chronic suboptimal nutrition (CSN. In this study energy expenditure (EE; kcal/100 g body weight and physical activity (PA; oscillations in weight/min/kg body weight were assessed in rats subjected to three levels of CSN. Results Body weight gain was diminished (76.7 ± 12.0 and 61.6 ± 11.0 g in rats fed 70 and 60% of the ad-libitum fed controls which gained more weight (148.5 ± 32.3 g. The rats fed 80% gained weight similarly to controls (136.3 ± 10.5 g. Percent Fat-free body mass was reduced (143.8 ± 8.7 and 142.0 ± 7.6 g in rats fed 70 and 60% of ad-libitum, but not in those fed 80% (200.8 ± 17.5 g as compared with controls (201.6 ± 33.4 g. Body fat (g decreased in rats fed 80% (19.7 ± 5.3, 70% (15.3 ± 3.5 and 60% (9.6 ± 2.7 of ad-libitum in comparison to controls (26.0 ± 6.7. EE and PA were also altered by CSN. The control rats increased their EE and PA during the dark periods by 1.4 ± 0.8 and 1.7 ± 1.1 respectively, as compared with light the period; whereas CSN rats fed 80 and 70% of ad-libitum energy intake had reduced EE and PA during the dark periods as compared with the light period EE(7.5 ± 1.4 and 7.8 ± 0.6 vs. 9.0 ± 1.2 and 9.7 ± 0.8; p Conclusion CSN rats adapt to mild energy restriction by reducing body fat, EE and PA mainly during the dark period while growth proceeds and lean body mass is preserved. At higher levels of energy restrictions there is decreased growth, body fat and lean mass. Moreover EE and PA are also reduced during both light and dark periods.

  2. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    Science.gov (United States)

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  3. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sheila Marques Fernandes

    2016-01-01

    Full Text Available Iodinated contrast (IC is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI. Chronic kidney disease (CKD and chronic hyperglycemia (CH are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH; Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  4. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs

    Directory of Open Access Journals (Sweden)

    Ronaldo Lopes Torres

    2014-06-01

    Full Text Available Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO and total reactive antioxidant potential (TRAP, in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.; acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days; and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

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

    Science.gov (United States)

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

    2012-01-01

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

  6. Bone metabolism of male rats chronically exposed to cadmium

    International Nuclear Information System (INIS)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina

    2005-01-01

    Recently, based on a female rat model of human exposure, we have reported that low-level chronic exposure to cadmium (Cd) has an injurious effect on the skeleton. The purpose of the current study was to investigate whether the exposure may also affect bone metabolism in a male rat model and to estimate the gender-related differences in the bone effect of Cd. Young male Wistar rats received drinking water containing 0, 1, 5, or 50 mg Cd/l for 12 months. The bone effect of Cd was evaluated using bone densitometry and biochemical markers of bone turnover. Renal handling of calcium (Ca) and phosphate, and serum concentrations of vitamin D metabolites, calcitonin, and parathormone were estimated as well. At treatment with 1 mg Cd/l, corresponding to the low environmental exposure in non-Cd-polluted areas, the bone mineral content (BMC) and density (BMD) at the femur and lumbar spine (L1-L5) and the total skeleton BMD did not differ compared to control. However, from the 6th month of the exposure, the Z score BMD indicated osteopenia in some animals and after 12 months the bone resorption very clearly tended to an increase. The rats' exposure corresponding to human moderate (5 mg Cd/l) and especially relatively high (50 mg Cd/l) exposure dose- and duration-dependently disturbed the processes of bone turnover and bone mass accumulation leading to formation of less dense than normal bone tissue. The effects were accompanied by changes in the serum concentration of calciotropic hormones and disorders in Ca and phosphate metabolism. It can be concluded that low environmental exposure to Cd may be only a subtle risk factor for skeletal demineralization in men. The results together with our previous findings based on an analogous model using female rats give clear evidence that males are less vulnerable to the bone effects of Cd compared to females

  7. BLOOD AMMONIA AND GLUTAMINE AS PREDICTORS OF HYPERAMMONEMIC CRISES IN UREA CYCLE DISORDER PATIENTS

    Science.gov (United States)

    Lee, Brendan; Diaz, George A.; Rhead, William; Lichter-Konecki, U.; Feigenbaum, Annette; Berry, Susan A.; Le Mons, C.; Bartley, James A; Longo, Nicola; Nagamani, Sandesh C.; Berquist, William; Gallagher, Renata; Bartholomew, Dennis; Harding, Cary O.; Korson, Mark S.; McCandless, Shawn E.; Smith, Wendy; Cederbaum, Stephen; Wong, Derek; Merritt, J. Lawrence; Schulze, A.; Vockley, Gerard.; Kronn, David; Zori, Roberto; Summar, Marshall; Milikien, D.A.; Marino, M.; Coakley, D.F.; Mokhtarani, M.; Scharschmidt, B.F.

    2014-01-01

    Purpose To examine predictors of ammonia exposure and hyperammonemic crises (HAC) in patients with urea cycle disorders (UCDs). Methods The relationships between fasting ammonia, daily ammonia exposure, and HACs were analyzed in >100 UCD patients. Results Fasting ammonia correlated strongly with daily ammonia exposure (r=0.764, p200% (purea nitrogen. Fasting glutamine correlated weakly with AUC0-24 and was not a significant predictor of HACs. Conclusions Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of HACs, suggesting that UCD patients may benefit from tight ammonia control. PMID:25503497

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

    van Koppen, Arianne; Papazova, Diana A.; Oosterhuis, Nynke R.; Gremmels, Hendrik; Giles, Rachel H.; Fledderus, Joost O.; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

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

  10. Chronic inflammation modulates ghrelin levels in humans and rats.

    Science.gov (United States)

    Otero, M; Nogueiras, R; Lago, F; Dieguez, C; Gomez-Reino, J J; Gualillo, O

    2004-03-01

    The aim of this work was to investigate whether changes in plasma ghrelin, the recently discovered 28-amino acid gastric hormone that regulates growth hormone (GH) secretion and energy homeostasis, occur during inflammation in adjuvant-induced arthritis (AA) in rats. For completeness, ghrelin plasma levels were measured in rheumatoid arthritis (RA) patients. AA was induced in male Lewis rats using Freund's complete adjuvant. Animals were monitored for weight and food intake, every 2 or 3 days, along all time-course experiments. Plasma ghrelin concentrations in 31 RA patients and 18 healthy controls, as well as in rats, were determined by a specific double-antibody radioimmunoassay. Gastric ghrelin mRNA expression was evaluated by northern blot analysis. Human GH and insulin-like growth factor (IGF)-1 were determined by quantitative chemiluminescence assay. Compared with controls, arthritic rats gained significantly (P Ghrelin plasma levels were significantly lower at day 7 after arthritis induction than in controls (AA 7 = 91.2 +/- 5.6 pg/ml vs controls = 124.75 +/- 5.9 pg/ml), but they recovered to control levels by day 15. RA patients had ghrelin plasma levels significantly lower than healthy controls (RA = 24.54 +/- 2.57 pg/ml vs 39.01 +/- 4.47 pg/ml of healthy controls; P = 0.0041). In AA, there is a compensatory variation of ghrelin levels that relates to body weight adjustments. Recovery of ghrelin levels in the latter stage suggests an adaptive response and may represent a compensatory mechanism under catabolic conditions. In RA patients, chronic imbalance in ghrelin levels suggests that this gastric hormone may participate, together with other factors, in alterations of metabolic status during inflammatory stress.

  11. Multidisciplinary management of ornithine transcarbamylase (OTC) deficiency in pregnancy: essential to prevent hyperammonemic complications

    Science.gov (United States)

    Lamb, Stephanie; Aye, Christina Yi Ling; Murphy, Elaine; Mackillop, Lucy

    2013-01-01

    Ornithine transcarbamylase (OTC) deficiency is the most common inborn error in the metabolism of the urea cycle with an incidence of 1 in 14 000 live births. Pregnancy can trigger potentially fatal hyperammonemic crises. We report a successful pregnancy in a 29-year-old primiparous patient with a known diagnosis of OTC deficiency since infancy. Hyperammonemic complications were avoided due to careful multidisciplinary management which included a detailed antenatal, intrapartum and postnatal plan. Management principles include avoidance of triggers, a low-protein diet and medications which promote the removal of nitrogen by alternative pathways. Triggers include metabolic stress such as febrile illness, particularly gastroenteritis, fasting and any protein loading. In our case the patient, in addition to a restricted protein intake, was prescribed sodium benzoate 4 g four times a day, sodium phenylbutyrate 2 g four times a day and arginine 500 mg four times a day to aid excretion of ammonia and reduce flux through the urea cycle. PMID:23283608

  12. Curative effect of sesame oil in a rat model of chronic kidney disease.

    Science.gov (United States)

    Liu, Chuan-Teng; Chien, Se-Ping; Hsu, Dur-Zong; Periasamy, Srinivasan; Liu, Ming-Yie

    2015-12-01

    Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. © 2015 Asian Pacific Society of Nephrology.

  13. The effects of acute and chronic estrogen deficiency on glucose and lipid profile in ovariectomized rats

    OpenAIRE

    Rabie P; Namjoo AR

    2017-01-01

    Background and aims: Ovariectomy is a standard experimental model of menopause in rodent to investigate postmenopausal women. The aim of this study was to evaluate effects acute and chronic estrogen deficiency on lipid profile and glucose serum in ovariectomized (OVX) rats. Methods: In this experimental study, Twenty-four adult female Wistar rats were divided into three groups of eight rats. The first group: sham-control, Second group: ovariectomized rats (for five weeks), Third group: Ova...

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

    International Nuclear Information System (INIS)

    Kent, R.L.; Lutzner, M.A.; Hansen, C.T.

    1976-01-01

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

  15. Chronic irradiation of gonad tissue of the male rat

    International Nuclear Information System (INIS)

    Lemaire, G.; Maas, J.

    1982-01-01

    The effects of chronically irradiating rats' testes with daily gamma radiation doses of (1.4 - 8.6) x 10 -2 Gy for 71-140 days were studied. After about 30 days irradiation, the testes weights decrease and level off at about 75 days. Irradiation also caused the germ cells in the seminiferous tubules to disappear progressively, completely when the dose exceeded 6 x 10 -2 Gy/day and partially with the lower doses. At doses below 6 x 10 -2 Gy/day, there was also a delay in the spermatogenesis cycle with the spermatogonia and spermatocytes appearing to reach a new equilibrium, the level of which depended on the dose. (U.K.)

  16. Severe diffuse axon injury in chronic alcoholic rat medulla oblongata following a concussion blow.

    Science.gov (United States)

    Luo, Jianming; Chen, Guang; Wei, Lai; Qian, Hong; Lai, Xiaoping; Wang, Dian; Lv, Junyao; Yu, Xiaojun

    2014-01-01

    We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

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

    Directory of Open Access Journals (Sweden)

    ZHANG Yi-dan

    2012-04-01

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

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

    Data.gov (United States)

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

  19. Effects of pudendal neuromodulation on bladder function in chronic spinal cord-injured rats

    Directory of Open Access Journals (Sweden)

    Yin-Tsong Lin

    2016-09-01

    Conclusion: This study demonstrates the feasibility of using pudendal neuromodulation in chronic SCI rats. These results could aid in developing an advanced neural prosthesis to restore bladder function in clinical settings.

  20. Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.

    Science.gov (United States)

    Gaudet, Andrew D; Ayala, Monica T; Schleicher, Wolfgang E; Smith, Elana J; Bateman, Emily M; Maier, Steven F; Watkins, Linda R

    2017-09-01

    Spinal cord injury (SCI) causes chronic pain in 65% of individuals. Unfortunately, current pain management is inadequate for many SCI patients. Rodent models could help identify how SCI pain develops, explore new treatment strategies, and reveal whether acute post-SCI morphine worsens chronic pain. However, few studies explore or compare SCI-elicited neuropathic pain in rats. Here, we sought to determine how different clinically relevant contusion SCIs in male and female rats affect neuropathic pain, and whether acute morphine worsens later chronic SCI pain. First, female rats received sham surgery, or 150kDyn or 200kDyn midline T9 contusion SCI. These rats displayed modest mechanical allodynia and long-lasting thermal hyperalgesia. Next, a 150kDyn (1s dwell) midline contusion SCI was performed in male and female rats. Interestingly, males, but not females showed SCI-elicited mechanical allodynia; rats of both sexes had thermal hyperalgesia. In this model, acute morphine treatment had no significant effect on chronic neuropathic pain symptoms. Unilateral SCIs can also elicit neuropathic pain that could be exacerbated by morphine, so male rats received unilateral T13 contusion SCI (100kDyn). These rats exhibited significant, transient mechanical allodynia, but not thermal hyperalgesia. Acute morphine did not exacerbate chronic pain. Our data show that specific rat contusion SCI models cause neuropathic pain. Further, chronic neuropathic pain elicited by these contusion SCIs was not amplified by our course of early post-trauma morphine. Using clinically relevant rat models of SCI could help identify novel pain management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

    OpenAIRE

    Desjardins , Stephane; Belkai , Emilie; Crete , Dominique; Cordonnier , Laurie; Scherrmann , Jean-Michel; Noble , Florence; Marie-Claire , Cynthia

    2008-01-01

    International audience; Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, th...

  2. Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats

    International Nuclear Information System (INIS)

    Seacat, Andrew M.; Thomford, Peter J.; Hansen, Kris J.; Clemen, Lisa A.; Eldridge, Sandra R.; Elcombe, Cliff R.; Butenhoff, John L.

    2003-01-01

    Perfluorooctanesulfonate (PFOS) is a widely disseminated persistent compound found at low (part-per-billion) concentrations in serum and liver samples from humans and fish-eating wildlife. This study investigated the hypotheses that early hepatocellular peroxisomal proliferation and hepatic cellular proliferation are factors in chronic liver response to dietary dosing, that lowering of serum total cholesterol is an early clinical measure of response to treatment, and that liver and serum PFOS concentrations are proportional to dose and cumulative dose after sub-chronic treatment. PFOS was administered in diet as the potassium salt at 0, 0.5, 2.0, 5.0, and 20 parts per million (ppm) to Sprague Dawley rats for 4 or 14 weeks. At 4 weeks, effects included decreased serum glucose and an equivocal (< twofold) increase in hepatic palmitoyl CoA oxidase (PCoAO) activity in 20 ppm dose-group males and elevation of alanine aminotransferase (ALT) in 20 ppm dose-group females. At 14 weeks, the 20 ppm males had increased liver weight, decreased serum cholesterol, increased non-segmented neutrophils, and increased ALT. Relative liver weights and urea nitrogen were increased in both sexes at 14 weeks. Hepatocytic hypertrophy and cytoplasmic vacuolation were observed in the 5 or 20 ppm male and the 20 ppm female dose groups. An increase in hepatic PCoAO activity was not observed at 14 weeks, and the average hepatocyte proliferation index was not increased, although, individual animals had mild increases. Serum and liver PFOS concentrations were proportional to dose and cumulative dose. Serum concentrations were generally higher in females than in males. The liver-to-serum PFOS ratios ranged from approximately 3:1 to 12:1. After 14 weeks, the no-observed-adverse effect level (NOAEL) in males and females was 5 ppm. The NOAEL corresponded to mean serum PFOS concentrations of 44 ppm (μg/ml) in males and 64 ppm in females and mean liver PFOS concentrations of 358 ppm in males and 370

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

    Directory of Open Access Journals (Sweden)

    Heloísa Aparecida Barbosa da Silva Pereira

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

  4. Oxaliplatin-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Pancreatic Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Takatsugu Ogata

    2017-10-01

    Full Text Available Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancreatic adenocarcinoma with peritoneal dissemination. GEMOX consists of gemcitabine (1,000 mg/m2 and oxaliplatin (100 mg/m2 on day 1, repeated every 2 weeks. The second cycle of GEMOX was administered as planned. However, he appeared to have difficulties with daily activities. Two days later, he visited the emergency room complaining of drowsiness. On examination, the patient had a Glasgow Coma Scale (GCS score of 14 (E4V4M6, and asterixis was not present. Blood examination revealed a serum ammonia level of 202 µg/dL. The levels of serum hepatic enzymes were only mildly elevated, and the hemoglobin level was typical for this patient. Computed tomography, magnetic resonance imaging, lumbar puncture test, and blood culture showed no abnormality. Based on these results, he was diagnosed with oxaliplatin-induced hyperammonemia. One day after hospitalization, GCS score had significantly decreased to 6 (E1V1M4. His consciousness disorder improved after administration of a nutritional supplement containing a high concentration of branched-chain amino acids for 5 days, and the level of serum ammonia improved to 79 µg/dL. He stated that he could not remember the episode. The findings of this case suggest the importance of examining serum ammonia levels in patients receiving an oxaliplatin-containing regimen who develop disordered consciousness.

  5. Hemodynamic characterization of chronic bile duct-ligated rats: effect of pentobarbital sodium

    International Nuclear Information System (INIS)

    Lee, S.S.; Girod, C.; Braillon, A.; Hadengue, A.; Lebrec, D.

    1986-01-01

    Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output and portal tributary blood flow. Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. The authors conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminated the hyperdynamic circulation

  6. Enhancing effects of chronic lithium on memory in the rat.

    Science.gov (United States)

    Tsaltas, Eleftheria; Kontis, Dimitrios; Boulougouris, Vasileios; Papakosta, Vasiliki-Maria; Giannou, Haralambos; Poulopoulou, Cornelia; Soldatos, Constantine

    2007-02-12

    In spite of recent enrichment of neurochemical and behavioural data establishing a neuroprotective role for lithium, its primary effects on cognitive functioning remain ambiguous. This study examines chronic lithium effects on spatial working memory and long-term retention. In three discrete experiments, rats subjected to 30 daily intraperitoneal injections (2mmol/kg) of lithium (lithium groups: serum lithium=0.5+/-0.4mEq/l, 12h post-injection) or saline (controls) were trained in 0-s delay T-maze alternation and then tested in 30-, 45- and 60-s delay alternation (Experiments 1, 2, 3, respectively). Animals from Experiment 1 were further tested in one-trial step-through passive avoidance under mild shock parameters (0.5mA, 1s). Retention was assessed 6h later. Daily lithium or saline injections continued throughout behavioural testing. Lithium animals were indistinguishable from controls during 0-delay alternation baseline (Experiments 1-3, accuracy>88%) but showed significantly higher accuracy than controls at 30- and 45-s delays (93% versus 85% and 92% versus 82%, Experiments 1 and 2, respectively). At 60-s delay (Experiment 3) this beneficial effect of lithium was no longer apparent (lithium and control accuracy=78%). In Experiment 4, the shock used did not support 6-h passive avoidance retention in controls, whereas lithium animals showed significant step-through latency increases. Chronic lithium enhanced spatial working memory and promoted long-term retention of a weak aversive contingency. The results suggest that lithium may have potential as a cognitive enhancer.

  7. Effect of atracylodes rhizome polysaccharide in rats with adenine-induced chronic renal failure.

    Science.gov (United States)

    Yang, C; Liu, C; Zhou, Q; Xie, Y C; Qiu, X M; Feng, X

    2015-01-01

    The aim of the study was to elucidate the therapeutic effects of Atracylodes rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10 rats per group): The normal control group, the chronic renal failure pathological control group, the dexamethasone treatment group and two Atracylodes rhizome polysaccharide treatment groups, treated with two different concentrations of the polysaccharide, the Atracylodes rhizome polysaccharide high group and the Atracylodes rhizome polysaccharide low group. All the rats, except those in the normal control group were fed adenine-enriched diets, containing 10 g adenine per kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome polysaccharide low group rats were administered the drug orally for 2 weeks. On day 35, the kidney coefficient of the rats and the serum levels of creatinine, blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to experimentation on a model of chronic renal failure in rats, the preparation was proven to be able to reduce serum levels of creatinine, blood urea nitrogen and hemalbumin levels (Prenal function. Atracylodes rhizome polysaccharide had reversed the majority of the indices of chronic renal failure in rats.

  8. Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

    Science.gov (United States)

    Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

    2014-08-01

    Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

  9. Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Wang, X-J; Xia, L-L; Xu, T-Y; Zhang, X-H; Zhu, Z-W; Zhang, M-G; Liu, Y; Xu, C; Zhong, S; Shen, Z-J

    2016-04-01

    There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats. © 2015 Blackwell Verlag GmbH.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Graebe, M.; Brond, L.; Christensen, S.

    2004-01-01

    The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligation...... (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were...

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

    Science.gov (United States)

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

    2016-05-01

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

  13. Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.

    Science.gov (United States)

    Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E

    2015-01-01

    To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

  14. Effects of acute and chronic uremia on active cation transport in rat myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Druml, W.; Kelly, R.A.; England, B.K.; O' Hara, D.S.; Mitch, W.E. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  15. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

    International Nuclear Information System (INIS)

    Sorrell, M.F.; Nauss, J.M.; Donohue, T.M. Jr.; Tuma, D.J.

    1983-01-01

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate [ 14 C]glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring [ 14 C]leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, [ 14 C]fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration

  16. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Cryz, S J

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O-polysacc......In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O......-polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared...... predominantly PMNs (TH2-like) to a chronic-type inflammation dominated by mononuclear leukocytes (TH1-like). In accordance, the antibody titers induced by the D-ALG toxin A vaccine were not different from those of the control rats after challenge. This study identifies a possible new way of modifying...

  17. [The expression and significance of VIP and its receptor in the cochlea of different degrees of chronic alcoholism rats].

    Science.gov (United States)

    Feng, Jing; Liu, Haibing

    2015-07-01

    To determine whether chronic alcoholism alters the expression levels of Vasoactive intestinal polypeptide (VIP) and its receptor (VIPR1) in the cochlea of chronic alcoholism rats. We measured their expression levels in 30 SD rats, in which we created models of different degrees of chronic alcoholism. We investigated the presence of the mRNA of VIP in the cochlea of chronic alcoholism rats and controls by reverse transcription-polymerase chain reaction (RT-PCR) method. We investigated the presence of proteins of VIPR1 in poisoned rats and controls by western blot. We also evaluated the local distribution of VIP cells by immunohistochemistry. We found that the levels of VIP and VIPR1 were downregulated in the chronic alcoholism groups compared to the controls group. The differences in some expression levels were significant different between chronic alcoholism rats and control rats. Moreover, at different degrees of alcohol poisoning in rats, the contents of VIP and VIPR1 differed. Decreased levels of VIP and VIPR1 were detected in the deep chronic alcoholism group compared to the group with low-degree poisoning (P 0.05). These results suggest that VIP and VIPR1 play an important role in the auditory function in rats with chronic alcoholism. Chronic alcoholism may cause a peptide hormone secretion imbalance in the auditory system, eventually leading to hearing loss.

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

    Directory of Open Access Journals (Sweden)

    M. Surekha Bhat

    2007-01-01

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

  19. Influence of chronic stress and oclusal interference on masseter muscle pain in rat.

    Science.gov (United States)

    Simonić-Kocijan, Suncana; Uhac, Ivone; Braut, Vedrana; Kovac, Zoran; Pavicić, Daniela Kovacević; Fugosić, Vesna; Urek, Miranda Muhvić

    2009-09-01

    This study aimed to investigate the individual effects of chronic stress and occlusal interference, as well as their combined influence on masseter muscle pain. Experiments were performed on 28 male Wistar rats. Animals were submitted to chronic stress procedure, exposed to occlusal interference, or exposed to both mantioned procedures. At the end of the procedure animals were submitted to orofacial formalin test, and nociceptive behavioral response was evaluated. Statisticaly significant difference of nociceptive behavioral response in chronicaly stressed rats and in the animals with occlusal interference in comparation to the control group were not obtained (p > 0.05). In contrast, nociceptive behavioral response was significantly increased in rats submitted to both of experimental procedures (p occlusal interference and chronic stress influence masseter muscle pain.

  20. 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.

  1. Effect of Xiaoyaosan Decoction on Learning and Memory Deficit in Rats Induced by Chronic Immobilization Stress

    OpenAIRE

    Meng, Zhen-Zhi; Chen, Jia-Xu; Jiang, You-Ming; Zhang, Han-Ting

    2013-01-01

    Xiaoyaosan (XYS) decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS). In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS) induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body w...

  2. CHRONIC ALCOHOLISM ON THE SEMINAL VESICLE AND TESTIS WEIGHT OF ADULT RATS (Rattus norvegicus)

    OpenAIRE

    Martinez, F. E.; Martinez, M.; Cagnon, V. H. A.; Mello Junior, W.; Padovani, C. R.; Garcia, P. J.

    1997-01-01

    Effects of experimental chronic alcoholism on the accessory sexual glands weight and testes weight were studied. Male adult albino rats received only sugar cane brandy at 30 Gay Lussac (v/v), while the controls received tap water. After periods of 60, 120, 180 and 240 days, rats from each group were anesthetized, weighed and sacrificed. Alterations in mean daily solid food intake and liquid, mean daily weight gain, mean prostate weight, mean seminal vesicle and coagulating gland weights and t...

  3. Effects of chronic lead intoxication on rat serotoninergic system and anxiety behavior.

    Science.gov (United States)

    Sansar, Wafa; Bouyatas, My Mustapha; Ahboucha, Samir; Gamrani, Halima

    2012-01-01

    Chronic lead exposure has been shown to produce behavioral disturbances in human and animal models. These disturbances are associated with alterations in monoaminergic neurotransmission in the central nervous system (CNS), some of which have been attributed to serotonin (5-HT). This study was undertaken to investigate the chronic effects of lead exposure on the serotoninergic system in the dorsal raphe nucleus (DRN) and the consequences of its toxicity on rat behavior. Adult male Wistar rats were chronically exposed for 3 months to 0.5% lead acetate in drinking water. The serotoninergic system was evaluated using immunohistochemistry and the anxiety behavior was assessed by the light/dark box test. The results show that chronic lead exposure induces a significant increase of blood and brain lead levels in treated rats compared with controls. The density of the immunoreactive serotoninergic cell bodies was significantly higher in treated rats in all parts of the DRN. Assessment of animal behavior using the light/dark box test showed that lead-treated rats spent significantly more time in the light chamber compared with controls (P=0.001). These findings suggest that lead exposure may possibly induce increased anxiety as a consequence of changes in neuronal 5-HT content in the DRN. Copyright © 2011 Elsevier GmbH. All rights reserved.

  4. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Directory of Open Access Journals (Sweden)

    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  5. Incorporation and distribution of tritium in rats after chronic exposure to various tritiated compounds

    International Nuclear Information System (INIS)

    Takeda, H.

    1991-01-01

    Rats were chronically exposed to tritiated water ( 3 HHO) and several tritiated organic compounds ([ 3 H]leucine, [ 3 H]lysine, [ 3 H]glucose, [ 3 H]glucosamine, [ 3 H]thymidine and [ 3 H]uridine) dissolved in their drinking water. An analysis of tritium in wet and dry tissues of rats at the end of 22 days' chronic exposure showed that the chemical form of the ingested tritium was more important for tritium uptake in dry tissues than in wet tissues. The highest concentrations of OBT (organically bound tritium) were found in rats exposed to tritiated amino acids ([sup (3)/H]lysine and [ 3 H]leucine), 4-9 times higher than those in rats exposed to 3 HHO. The next highest concentrations were found in rats exposed to [ 3 H]uridine., The result of radiation dose estimations at the end of chronic exposure showed the contribution of OBT to total dose rate was higher in the tissues of rats exposed to tritiated organic compounds than that after exposure to 3 HHO. The differences between total dose rates from 3 HHO and those from tritiated organic compounds were within a factor of 2. (author)

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

    Directory of Open Access Journals (Sweden)

    LJUBICA GAVRILOVIC

    2013-09-01

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

  7. Acute and chronic ethanol intake: effects on spatial and non-spatial memory in rats.

    Science.gov (United States)

    García-Moreno, Luis M; Cimadevilla, Jose M

    2012-12-01

    Abusive alcohol consumption produces neuronal damage and biochemical alterations in the mammal brain followed by cognitive disturbances. In this work rats receiving chronic and acute alcohol intake were evaluated in a spontaneous delayed non-matching to sample/position test. Chronic alcohol-treated rats had free access to an aqueous ethanol solution as the only available liquid source from the postnatal day 21 to the end of experiment (postnatal day 90). Acute alcoholic animals received an injection of 2 g/kg ethanol solution once per week. Subjects were evaluated in two tests (object recognition and spatial recognition) based on the spontaneous delayed non-matching to sample or to position paradigm using delays of 1 min, 15 min and 60 min. Results showed that chronic and acute alcohol intake impairs the rats' performance in both tests. Moreover, chronic alcohol-treated rats were more altered than acute treated animals in both tasks. Our results support the idea that chronic and acute alcohol administration during postnatal development caused widespread brain damage resulting in behavioral disturbances and learning disabilities. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Hypercaloric diet modulates effects of chronic stress: a behavioral and biometric study on rats.

    Science.gov (United States)

    Oliveira, Carla de; Oliveira, Cleverson Moraes de; de Macedo, Isabel Cristina; Quevedo, Alexandre S; Filho, Paulo Ricardo Marques; Silva, Fernanda Ribeiro da; Vercelino, Rafael; de Souza, Izabel C Custodio; Caumo, Wolnei; Torres, Iraci L S

    2015-01-01

    Obesity is a chronic disease that has been associated with chronic stress and hypercaloric diet (HD) consumption. Increased ingestion of food containing sugar and fat ingredients (comfort food) is proposed to "compensate" chronic stress effects. However, this eating habit may increase body fat depositions leading to obesity. This study evaluated behavioral/physiological parameters seeking to establish whether there is an association between the effects of HD intake and stress, and to test the hypothesis that the development of anxious behavior and obesity during chronic stress periods depends on the type of diet. Sixty-day-old male Wistar rats (n = 100) were divided into four groups: standard chow, hypercaloric diet, chronic stress/standard chow and chronic stress/hypercaloric diet. Chronic stress was induced by restraint stress exposure for 1 h/day, for 80 d. At the end of this period, rat behavior was evaluated using open-field and plus-maze tests. The results showed that HD alone increased weight gain and adipose deposition in subcutaneous and mesenteric areas. However, stress reduced weight gain and adipose tissue in these areas. HD also increased naso-anal length and concurrent stress prevented this. Behavioral data indicated that stress increased anxiety-like behaviors and comfort food reduced these anxiogenic effects; locomotor activity increased in rats fed with HD. Furthermore, HD decreased corticosterone levels and stress increased adrenal weight. The data indicate that when rats are given HD and experience chronic stress this association reduces the pro-obesogenic effects of HD, and decreases adrenocortical activity.

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

    OpenAIRE

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

    2009-01-01

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

  10. Functional activity of symphathetic-adrenal system under chronic and fractionated irradiation of rats

    International Nuclear Information System (INIS)

    Musagalieva, G.M.

    1975-01-01

    Chronic irradiation of rats at 5 R twice a week (total dose 400 R) significantly increased adrenaline concentration in the brain, liver and kidney and dophamine and DOPA concentration in liver tissue, adrenal glands and thymus. Fractionated irradiation (chronic irradiation at 400 R plus acute single irradiation at 400 R) increased the adrenaline level in the brain and heart muscle and led to a higher concentration of dophamine and DOPA in the liver, thymus and heart muscle [ru

  11. Pair-housing of male and female rats during chronic stress exposure results in gender-specific behavioral responses

    NARCIS (Netherlands)

    Westenbroek, C.; Snijders, T.A.B.; Den Boer, J.A.; Gerrits, Marjolein; Fokkema, D.S.; ter Horst, G.J

    Social support has a positive influence on the course of a depression and social housing of rats could provide an animal model for studying the neurobiological mechanisms of social support. Male and female rats were subjected to chronic footshock stress for 3 weeks and pair-housing of rats was used

  12. Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Rygaard, J

    1996-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal ch...

  13. Dental and oropharyngeal lesions in rats with chronic acid reflux esophagitis.

    Science.gov (United States)

    Shimazu, Rintaro; Yamamoto, Mihoko; Minesaki, Akimichi; Kuratomi, Yuichiro

    2018-06-01

    In this study, we evaluated pathological changes in the tooth and pharynx of GERD rats to elucidate the association between gastric acid reflux and oral and pharyngeal diseases. An experimental rat model of chronic acid reflux esophagitis was surgically created. The oral cavities were observed histologically every 2 weeks until 20 weeks after surgery. At 10 weeks after surgery, molar crown heights in GERD rats were shorter than that in control rats, and inflammatory cell infiltration by gastric acid reflux was found in the periodontal mucosa of GERD rats. Furthermore, dental erosion progressed in GERD rats at 20 weeks after surgery, and enamel erosion and dentin exposure were observed. During the same period, inflammatory cell infiltration was observed in the mucosa of the posterior part of the tongue. These findings suggest that gastric acid reflux may be one of the exacerbating factors of dental erosion, periodontitis and glossitis. We investigated oral changes in an experimental rat model of GERD and observed development of dental erosion, periodontitis and glossitis. Our findings suggested chronic gastric acid reflux may be involved in the pathogenesis of oral disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity.

    Science.gov (United States)

    Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang

    2015-06-21

    To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7(th) week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P 0.05). Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.

  15. HISTOLOGICAL EFFECTS OF CHRONIC CONSUMPTION OF NUTMEG ON THE LATERAL GENICULATE BODY OF ADULT WISTAR RATS.

    Directory of Open Access Journals (Sweden)

    J.O. Adjene

    2010-01-01

    Full Text Available The effects of chronic consumption of nutmeg commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the lateral geniculate body of adult wistar rats was studied.The rats of both sexes, with average weight of 200g were randomly assigned into treatment and control groups. The rats in the treatment group (n=8 received 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group (n=8 received equal amount of feeds daily without nutmeg added for thirty-two days. The growers mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo State, Nigeria and the rats were given water liberally. The rats were sacrificed on the thirty-three day of the experiment. The lateral geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological study.The findings indicate that rats in the treated group showed some cellular degenerative changes like sparse cellular population, pyknotic nuclei with some microcystic changes, edema and vacuolations in the stroma of the treated lateral geniculate body as compared to that of the control group.Chronic consumption of nutmeg may therefore have an adverse effect on the visual sensibilities by affecting the microanatomy of the lateral geniculate body of adult wistar rats. It is recommended for further studies aimed at corroborating these observations.

  16. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

    Science.gov (United States)

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

    2014-01-01

    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  17. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism.

    Science.gov (United States)

    Li, Shuang; Wang, S U; Guo, Zhi-Gang; Huang, Ning; Zhao, Fan-Rong; Zhu, Mo-Li; Ma, Li-Juan; Liang, Jin-Ying; Zhang, Yu-Lin; Huang, Zhong-Lin; Wan, Guang-Rui

    2015-11-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

  18. Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol-treated diabetic rats

    Directory of Open Access Journals (Sweden)

    Mi Ran Choi

    2017-10-01

    Conclusion: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

  19. Chronic aspiration of gastric and duodenal contents and their effects on inflammatory cytokine production in respiratory system of rats.

    OpenAIRE

    Mitra Samareh Fekri; Hamid Reza Poursalehi; Hamid Najafipour; Beydolah Shahouzahi; Nasrin Bazargan Harandi

    2014-01-01

    Gastroesophageal reflux disease (GERD) is defined with clinical symptoms of heart burning and regurgitation. It may be associated with external esophageal symptoms such as chronic cough, asthma, laryngitis, chronic lung disease, sinusitis and pulmonary fibrosis. In the present study, rats with chronic aspiration of gastroduodenal contents were studied for cellular phenotypes and cytokine concentrations in bronchoalveolar lavage and lung tissue. Thirty-six male Albino N-MRI rats were randomly ...

  20. Early histological and functional effects of chronic copper exposure in rat liver.

    Science.gov (United States)

    Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

    2005-10-01

    Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

  1. Very-low-density lipoprotein triglyceride kinetics in acute and chronic carbohydrate-fed rats

    International Nuclear Information System (INIS)

    Hirano, T.; Mamo, J.; Poapst, M.; Steiner, G.

    1988-01-01

    Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in rats maintained on either chow and water (control) or chow and a 10% carbohydrate drinking solution (fructose or glucose). The hexose solutions were available for an acute (16 h) or chronic (14 day) period. The acute fructose (AF), acute glucose (AG), and chronic fructose (CF) groups were hypertriglyceridemic (HTG) compared with control. Plasma TG concentration in chronic glucose (CG)-fed rats was similar to control. VLDL-TG was endogenously radiolabeled in donor rats with [2-3H]-glycerol. The fractional catabolic rate (FCR) was then determined by monitoring the clearance of plasma [3H]VLDL-TG in recipient animals. Donors and recipients were treated in an identical manner. AF and CF groups had an FCR significantly lower than rats given glucose for comparable periods. Both fructose groups and the AG group also had a lower FCR than control. In contrast, FCR in the CG group was significantly higher than controls. TG production rate (TGPR) in both AF and CF fed rats did not significantly differ from controls, suggesting that the HTG observed in these animals was solely from a catabolic defect. AG- and CG-treated glucose animals both had TGPR significantly higher than controls. Therefore, overproduction of VLDL-TG contributed to the HTG associated with this carbohydrate

  2. SYNAPTIC PLASTICITY IN THE DENTATE GYRUS OF AGED RATS IS ALTERED AFTER CHRONIC NIMODIPINE APPLICATION

    NARCIS (Netherlands)

    DEJONG, GI; BUWALDA, B; SCHUURMAN, T; LUITEN, PGM

    1992-01-01

    We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this

  3. Perinatal and chronic hypothyroidism impair behavioural development in male and female rats.

    NARCIS (Netherlands)

    Wijk, van N.; Rijntjes, E.; Heijning, van de B.J.

    2008-01-01

    Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. EXP PHYSIOL 00(0) 000-000, 0000. - A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the

  4. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats

    NARCIS (Netherlands)

    Waanders, Femke; Rienstra, Heleen; Boer, Mark Walther; Zandvoort, Andre; Rozing, Jan; Navis, Gerjan; van Goor, Harry; Hillebrands, Jan-Luuk

    Waanders F, Rienstra H, Walther Boer M, Zandvoort A, Rozing J, Navis G, van Goor H, Hillebrands JL. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats. Am J Physiol Renal Physiol 296: F1072-F1079, 2009. First published February 25, 2009;

  5. Chronic 14-day exposure to insecticides or methylmercury modulates neuronal activity in primary rat cortical cultures

    NARCIS (Netherlands)

    Dingemans, Milou; Schütte, Marijke G; Wiersma, Daphne M M; de Groot, Aart; van Kleef, Gina; Wijnolts, Fiona; Westerink, Remco

    2016-01-01

    There is an increasing demand for in vitro test systems to detect neurotoxicity for use in chemical risk assessment. In this study, we evaluated the applicability of rat primary cortical cultures grown on multi-well micro-electrode arrays (mwMEAs) to detect effects of chronic 14-day exposure to

  6. Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

    OpenAIRE

    Husain, Shahid; Abdul, Yasir; Crosson, Craig E.

    2012-01-01

    Morphine, a broad range opioid-receptors agonist, provides retina neuroprotection against glaucomatous injury in chronic experimental rat model. Morphine-induced retina neuroprotection in glaucoma model is mediated partly via inhibition of TNF-alpha production and caspase-3 and caspase-8 activation.

  7. Enhanced fear recall and emotional arousal in rats recovering from chronic variable stress.

    Science.gov (United States)

    McGuire, Jennifer; Herman, James P; Horn, Paul S; Sallee, Floyd R; Sah, Renu

    2010-11-02

    Emergence of posttraumatic-like behaviors following chronic trauma is of interest given the rising prevalence of combat-related posttraumatic stress disorder (PTSD). Stress associated with combat usually involves chronic traumatization, composed of multiple, single episode events occurring in an unpredictable fashion. In this study, we investigated whether rats recovering from repeated trauma in the form of chronic variable stress (CVS) express posttraumatic stress-like behaviors and dysregulated neuroendocrine responses. Cohorts of Long-Evans rats underwent a 7 day CVS paradigm followed by behavioral and neuroendocrine testing during early (16 h post CVS) and delayed (7 day) recovery time points. A fear conditioning-extinction-reminder shock paradigm revealed that CVS induces exaggerated fear recall to reminder shock, suggestive of potentiated fear memory. Rats with CVS experience also expressed a delayed expression of fearful arousal under aversive context, however, social anxiety was not affected during post-CVS recovery. Persistent sensitization of the hypothalamic-pituitary-adrenocorticotropic response to a novel acute stressor was observed in CVS exposed rats. Collectively, our data are consistent with the constellation of symptoms associated with posttraumatic stress syndrome, such as re-experiencing, and arousal to fearful contexts. The CVS-recovery paradigm may be useful to simulate trauma outcomes following chronic traumatization that is often associated with repeated combat stress. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Gong-ting CUI

    2014-08-01

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

  9. Effects of chronic delta-9-THC treatment on cardiac beta-adrenoceptors in rats

    Energy Technology Data Exchange (ETDEWEB)

    Evans, E.B.; Seifen, E.; Kennedy, R.H.; Kafiluddi, R.; Paule, M.G.; Scallet, A.C.; Ali, S.F.; Slikker, W. Jr.

    1987-10-01

    This study was designed to determine if chronic treatment with delta-9-tetrahydrocannabinol (THC) alters cardiac beta-adrenoceptors in the rat. Following daily oral administration of 10 or 20 mg/kg THC or an equivalent volume of control solvent for 90 days, rats were sacrificed, and sarcolemmal membranes were prepared from ventricular myocardium. Beta-adrenoceptor density and binding affinity estimated with (-)(/sup 3/H)dihydroalprenolol; a beta-adrenergic antagonist, were not significantly affected by treatment with THC when compared to vehicle controls. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.

  10. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment......, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone-related biochemistry was measured in serum and urine. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

  11. Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure.

    Science.gov (United States)

    Xu, Bo; Zheng, Hong; Patel, Kaushik P

    2012-04-15

    Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 ± 0.6 vs. 2.6 ± 0.3 spikes/s, P neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 ± 7% vs. +184 ± 61%) or an increase in MAP (-42 ± 8% vs. -71 ± 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 ± 15% vs. 92 ± 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to baroreceptor and osmotic challenges observed during CHF.

  12. Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

    International Nuclear Information System (INIS)

    Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

    2007-01-01

    Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

  13. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.

    Science.gov (United States)

    Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin

    2016-12-01

    Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

  14. Chronic prostatic infection and inflammation by Propionibacterium acnes in a rat prostate infection model.

    Science.gov (United States)

    Olsson, Jan; Drott, Johanna Bergh; Laurantzon, Lovisa; Laurantzon, Oscar; Bergh, Anders; Elgh, Fredrik

    2012-01-01

    Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic

  15. Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Samini, Mohammad; Farkhondeh, Tahereh

    2017-05-04

    Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

  16. Cognitive deficits in the rat chronic mild stress model for depression: relation to anhedonic-like responses

    DEFF Research Database (Denmark)

    Henningsen, Kim; Andreasen T., Jesper; Bouzinova, Elena V.

    2009-01-01

    in the spontaneous alternation test, possibly reflecting a deficit in working memory. This effect was independent of whether the stressed rats were anhedonic-like or stress-resilient as measured by their sucrose intake. CMS did not influence performance in passive avoidance and auditory cued fear conditioning......The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviours in laboratory rats. The aim of the present study was to examine the effects of chronic stress on cognitive performance. About 70% of rats exposed to 7 weeks of chronic mild stress showed a gradual reduction...... in consumption of a sucrose solution, indicating an anhedonic-like state. The remaining rats did not reduce their sucrose intake, but appeared resilient to the stress-induced effects on sucrose intake. Cognitive profiling of the CMS rats revealed that chronic stress had a negative effect on performance...

  17. Depression of biliary glutathione excretion by chronic ethanol feeding in the rat

    International Nuclear Information System (INIS)

    Vendemiale, G.; Jayatilleke, E.; Shaw, S.; Lieber, C.S.

    1984-01-01

    The effects of chronic alcohol feeding on biliary glutathione excretion were studied in rats pair fed diets containing either ethanol (36% of total energy) or isocaloric carbohydrate for 4-6 weeks. An exteriorized biliary-duodenal fistula was established and total glutathione (GSH) and oxidized glutathione (GSSG) were measured. A significant decrease was observed in rats fed alcohol chronically compared to their pair fed controls in the biliary excretion of GSH (55.7 +/- 37.0 vs 243.1 +/- 29.0 μg/ml bile, p 35 -L-methionine incorporation into hepatic and biliary GSH was unchanged or even increased after chronic ethanol feeding. 22 references, 4 figures

  18. Effects of chronic ethanol ingestion on arachidonic acid (AA) metabolism in rat macrophages

    International Nuclear Information System (INIS)

    Chanmugam, P.; Boudreau, M.; Hymel, G.; Jeffers, G.; Hwang, D.H.

    1986-01-01

    In a previous report, preincubation of rat platelets with ethanol resulted in dose dependent inhibition of AA metabolites whereas chronic ingestion of ethanol enhanced the synthesis of AA metabolites. Thus, the authors studied whether chronic ethanol ingestion also affects AA metabolism in MACS. Two groups of rats (10 each) were fed DeCarli/Lieber liquid diet containing 36 caloric % ethanol for 3 weeks. The control group was pair fed the same diet made isocaloric with dextrin-maltose. Resident MACS were collected by peritoneal lavage. The monolayers of MACS were incubated for 20 min with calcium ionophore (5μg/ml), and the incubation stopped with 4 vol. of ethanol. PGE 2 , LTB 4 and 5-HETE were assayed by radioimmunoassay. The results indicated that chronic ethanol ingestion did not affect the capacity of MACS to synthesize AA metabolites. There was also no difference in the levels of AA metabolites in heart and lung homogenates between the two groups

  19. Chronic Sleep Disturbance Impairs Glucose Homeostasis in Rats

    NARCIS (Netherlands)

    Barf, R. Paulien; Meerlo, Peter; Scheurink, Anton J. W.

    2010-01-01

    Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory

  20. Chronic loss of melanin-concentrating hormone affects motivational aspects of feeding in the rat.

    Directory of Open Access Journals (Sweden)

    Joram D Mul

    2011-05-01

    Full Text Available Current epidemic obesity levels apply great medical and financial pressure to the strenuous economy of obesity-prone cultures, and neuropeptides involved in body weight regulation are regarded as attractive targets for a possible treatment of obesity in humans. The lateral hypothalamus and the nucleus accumbens shell (AcbSh form a hypothalamic-limbic neuropeptide feeding circuit mediated by Melanin-Concentrating Hormone (MCH. MCH promotes feeding behavior via MCH receptor-1 (MCH1R in the AcbSh, although this relationship has not been fully characterized. Given the AcbSh mediates reinforcing properties of food, we hypothesized that MCH modulates motivational aspects of feeding.Here we show that chronic loss of the rat MCH-precursor Pmch decreased food intake predominantly via a reduction in meal size during rat development and reduced high-fat food-reinforced operant responding in adult rats. Moreover, acute AcbSh administration of Neuropeptide-GE and Neuropeptide-EI (NEI, both additional neuropeptides derived from Pmch, or chronic intracerebroventricular infusion of NEI, did not affect feeding behavior in adult pmch(+/+ or pmch(-/- rats. However, acute administration of MCH to the AcbSh of adult pmch(-/- rats elevated feeding behavior towards wild type levels. Finally, adult pmch(-/- rats showed increased ex vivo electrically evoked dopamine release and increased limbic dopamine transporter levels, indicating that chronic loss of Pmch in the rat affects the limbic dopamine system.Our findings support the MCH-MCH1R system as an amplifier of consummatory behavior, confirming this system as a possible target for the treatment of obesity. We propose that MCH-mediated signaling in the AcbSh positively mediates motivational aspects of feeding behavior. Thereby it provides a crucial signal by which hypothalamic neural circuits control energy balance and guide limbic brain areas to enhance motivational or incentive-related aspects of food consumption.

  1. Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat model

    Science.gov (United States)

    Somann, Jesse P.; Albors, Gabriel O.; Neihouser, Kaitlyn V.; Lu, Kun-Han; Liu, Zhongming; Ward, Matthew P.; Durkes, Abigail; Robinson, J. Paul; Powley, Terry L.; Irazoqui, Pedro P.

    2018-06-01

    Objective. Numerous studies of vagal nerve stimulation (VNS) have been published showing it to be a potential treatment for chronic inflammation and other related diseases and disorders. Studies in recent years have shown that electrical stimulation of the vagal efferent fibers can artificially modulate cytokine levels and reduce systematic inflammation. Most VNS research in the treatment of inflammation have been acute studies on rodent subjects. Our study tested VNS on freely moving animals by stimulating and recording from the cervical vagus with nerve cuff electrodes over an extended period of time. Approach. We used methods of electrical stimulation, retrograde tracing (using Fluorogold) and post necropsy histological analysis of nerve tissue, flow cytometry to measure plasma cytokine levels, and MRI scanning of gastric emptying. This novel combination of methods allowed examination of physiological aspects of VNS previously unexplored. Main results. Through our study of 53 rat subjects, we found that chronically cuffing the left cervical vagus nerve suppressed efferent Fluorogold transport in 43 of 44 animals (36 showed complete suppression). Measured cytokine levels and gastric emptying rates concurrently showed nominal differences between chronically cuffed rats and those tested with similar acute methods. Meanwhile, results of electrophysiological and histological tests of the cuffed nerves revealed them to be otherwise healthy, consistent with previous literature. Significance. We hypothesize that due to these unforeseen and unexplored physiological consequences of the chronically cuffed vagus nerve in a rat, that inflammatory modulation and other vagal effects by VNS may become unreliable in chronic studies. Given our findings, we submit that it would benefit the VNS community to re-examine methods used in previous literature to verify the efficacy of the rat model for chronic VNS studies.

  2. Hyperammonemia: What Urea-lly Need to Know: Case Report of Severe Noncirrhotic Hyperammonemic Encephalopathy and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ruby Upadhyay

    2016-01-01

    Full Text Available Purpose. A 66-year-old man who presented with coma was found to have isolated severe hyperammonemia and diagnosed with a late-onset urea-cycle disorder. He was treated successfully and had full recovery. Methods. We report a novel case of noncirrhotic hyperammonemia and review the literature on this topic. Selected literature for review included English-language articles concerning hyperammonemia using the search terms “hyperammonemic encephalopathy”, “non-cirrhotic encephalopathy”, “hepatic encephalopathy”, “urea-cycle disorders”, “ornithine transcarbamylase (OTC deficiency”, and “fulminant hepatic failure”. Results. A unique case of isolated hyperammonemia diagnosed as late-onset OTC deficiency is presented. Existing evidence about hyperammonemia is organized to address pathophysiology, clinical presentation, diagnosis, and treatment. The case report is discussed in context of the reviewed literature. Conclusion. Late-onset OTC deficiency presenting with severe hyperammonemic encephalopathy and extensive imaging correlate can be fully reversible if recognized promptly and treated aggressively.

  3. Sub-chronic lead exposure produces β1-adrenoceptor downregulation decreasing arterial pressure reactivity in rats.

    Science.gov (United States)

    Toscano, Cindy Medici; Simões, Maylla Ronacher; Alonso, Maria Jesus; Salaices, Mercedes; Vassallo, Dalton Valentim; Fioresi, Mirian

    2017-07-01

    Lead is considered a causative factor for hypertension and other cardiovascular diseases. To investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β 1 -adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo. Male Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days. Blood pressure in the Pb rats increased starting from the first week of treatment until the end of the study [systolic blood pressure, Ct: 122±4 vs. Pb: 143±3mmHg; diastolic blood pressure, Ct: 63±4 vs. Pb: 84±4mmHg]. The heart rate was also increased (Ct: 299±11 vs. Pb: 365±11bpm), but the pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats. Isoproterenol increased the left ventricular systolic and end-diastolic pressure, and heart rate only in Ct rats, suggesting that lead induced β 1 -adrenoceptor downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb rats, suggesting the involvement of cyclooxygenase-derived products (which are associated with reduced nitric oxide bioavailability) in this process. These findings offer further evidence that the effects of sub-chronic lead exposure in vitro can be reproduced in vivo-even at low concentrations-thus triggering mechanisms for the development of hypertension. Therefore, lead should be considered an environmental risk factor for cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. [Effects of polydatin on learning and memory and Cdk5 kinase activity in the hippocampus of rats with chronic alcoholism].

    Science.gov (United States)

    Li, Xin-juan; Zhang, Yan; Xu, Chun-yang; Li, Shuang; Du, Ai-lin; Zhang, Li-bin; Zhang, Rui-ling

    2015-03-01

    To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism. Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method. The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P chronic alcoholism group (P chronic alcoholism group( P chronic alcoholism group were significantly increased compared with control group (P chronic alcoholism group ( P chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.

  5. Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

    Directory of Open Access Journals (Sweden)

    Gloria E Hoffman

    Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

  6. Effect of chronic aspirin ingestion on epithelial proliferation in rat fundus, antrum, and duodenum

    International Nuclear Information System (INIS)

    Eastwood, G.L.; Quimby, G.F.

    1972-01-01

    We studied the effect of chronic aspirin ingestion on gastroduodenal epithelial proliferation by feeding rats aspirin in the drinking water. A control group of rats received plain water. At the end of 4 wk, [3H]-thymidine was given intravenously to label proliferating cells, and the rats were killed 1 h later. Sections of fundus, antrum, and proximal duodenum were processed for light autoradiography. We found that chronic aspirin ingestion stimulated epithelial proliferation in fundic mucosa but had no effect in the antrum. In the duodenum, aspirin increased proliferation in the lowest four crypt-cell positions, which most likely indicates an increase in stem-cell production. None of the tissues contained evidence of inflammation or ulceration. The proliferative effects of aspirin may help explain the previously observed phenomenon of mucosal adaptation in the rat after repeated exposure to aspirin. Further, if human gastroduodenal epithelium responds in a similar manner to chronic aspirin exposure, the effects on proliferation may explain in part the distribution of aspirin-associated ulcers

  7. Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

    Science.gov (United States)

    Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

    2017-02-05

    The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

    Science.gov (United States)

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  9. Establishment of a chronic activity-based anorexia rat model

    NARCIS (Netherlands)

    Frintrop, Linda; Trinh, Stefanie; Liesbrock, Johanna; Paulukat, Lisa; Kas, Martien J; Tolba, Rene; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2018-01-01

    BACKGROUND: Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of this

  10. Establishment of a chronic activity-based anorexia rat model

    NARCIS (Netherlands)

    Frintrop, Linda; Trinh, Stefanie; Liesbrock, Johanna; Paulukat, Lisa; Kas, Martien J.; Tolba, Rene; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2018-01-01

    AbstractBackground Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of

  11. An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats

    Directory of Open Access Journals (Sweden)

    M. Rodríguez-Martínez

    2010-11-01

    Full Text Available There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP and the heart rate (HR of all rats were measured systematically before (over 1 h and after three consecutive iv bolus injections of phenylephrine (PHE and sodium nitroprusside (SNP. Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI] and SNP-PHE slope [transformed general sensitivity index (TGSI, {((3-(ΔHRSNP-ΔHRPHE/ΔMAPSNP-ΔMAPPHE-0.4-1/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46, aortic (8.40 to 9.94 and sino-aortic (7.68 to 8.24 barodenervated conscious rats were defined.

  12. Chronic Rumex Patientia Seed Feeding Improves Passive Avoidance Learning and Memory in Streptozotocin-Diabetic Rats

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    Tourandokht Baluchnejadmojarad

    2010-08-01

    Full Text Available A B S T R A C T Introduction: Diabetes mellitus is accompanied with disturbances in learning, memory, and cognitive skills in the human society and experimental animals. Due to anti-diabetic and antioxidant activity of Rumex patientia (RP, this research study was conducted to evaluate the efficacy of chronic Rumex patientia feeding on alleviation of learning and memory disturbance in streptozotocindiabetic rats. Methods: Male Wistar rats were divided into control, diabetic, RP-treatedcontrol and -diabetic groups. For induction of diabetes, streptozotcin (STZ was administered at a dose of 60 mg/Kg. Meanwhile, RP-treated groups received RP seed powder mixed with standard pelleted food at a weight ratio of 6% for 4 weeks. For evaluation of learning and memory, initial latency (IL and step-through latency (STL were determined at the end of study using passive avoidance test. Results: It was found out that regarding initial latency, there was no significant difference among the groups. In addition, diabetic rats developed a significant impairment in retention and recall in passive avoidance test (p<0.01, as it is evident by a lower STL. Furthermore, RP treatment of diabetic rats did produce a significant improvement in retention and recall (p<0.05. Discussion: Taken together, chronic RP feeding could improve retention and recall capability in passive avoidance test in STZ-diabetic rats

  13. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment...... mass ex vivo.RESULTS: Most (90%) of the rats survived the study period (8 months); six rats died from bowel obstruction at the level of the entero-anastomosis and four had to be killed because of persistent severe diarrhoea. Vital intestinal mucosa was found in all augmented bladders. There were...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

  14. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Directory of Open Access Journals (Sweden)

    Xue-ying Chang

    2017-01-01

    Full Text Available Background. This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d, 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS/p38 mitogen activated protein kinase (p38MAPK pathway was determined to explore the potential mechanism. Results. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA and creatinine levels, malonaldehyde (MDA content, and superoxide dismutase (SOD activity in serum and the increases of calcium and alkaline phosphatase (ALP activity in the aorta (P<0.05 and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Experimental pulmonary fibrosis in rats with chronic gastric acid reflux esophagitis.

    Science.gov (United States)

    Shimazu, Rintaro; Aoki, Shigehisa; Kuratomi, Yuichiro

    2015-10-01

    To elucidate the association between gastric acid reflux and respiratory diseases by studying the histological changes of the lower airway in rats with chronic acid reflux esophagitis. An experimental rat model of chronic acid reflux esophagitis was surgically created. The lower airways of these rats were histologically observed for more than 50 weeks. Although there were no histological changes which induced gastric acid reflux at 10 weeks after surgery, thickening of the basal laminae and the proliferation of the collagenous fibers were observed in the alveolar epithelium at 20 weeks after surgery. At 50 weeks after surgery, the collagenous fibers obliterated the pulmonary alveoli and bronchial lumen. These findings observed in the GERD rats are similar to the pathological findings of human pulmonary fibrosis. In this study, we reported pathological changes in the lower airways of GERD rat models observed for more than 50 weeks. These results suggest that gastric acid reflux may be one of the pathogenic or exacerbating factors of pulmonary fibrosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

    Science.gov (United States)

    Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

    2017-01-01

    This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  18. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Science.gov (United States)

    Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

    2017-01-01

    Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

  19. Desipramine rescues age-related phenotypes in depression-like rats induced by chronic mild stress.

    Science.gov (United States)

    Xie, Xiaoxian; Chen, Yangyang; Wang, Qi; Shen, Qichen; Ma, Lingyan; Huang, Liangfeng; Wu, Tao; Fu, Zhengwei

    2017-11-01

    Our previous finding demonstrates that major depressive disorder can mediate accelerated aging in rats. Desipramine is a typical tricyclic antidepressant, and can provide neuroprotection and counteract depression-like behaviors. However, whether desipramine can rescue age-related phenotypes in depressed individuals is not understood. In the present study, we investigated the physiological function of desipramine on rescuing the age-related phenotypes in these animals. The rats were induced by chronic mild stress paradigm, and the depression-like behaviors of rats were detected by sucrose intake test, open field test (OFT) and forced swimming test (FST). Then the depressed rats were treated by desipramine. Desipramine administration was effective in counteracting depression-like behaviors by increasing the sucrose solution intake, reducing the immobility time in the FST, and increasing total distance travelled and numbers of grid line crossed in the OFT. Moreover, desipramine treatment was able to reduce the oxidative damage to rat liver, and to increase the expression of telomerase reverse transcriptase (TERT), leading to correspondingly restored telomerase activity. Our findings identify that one function of desipramine may partly be to rescue age-related phenotypes in depressed individuals induced by chronic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Characterizing the Effects of Chronic 2G Centrifugation on the Rat Skeletal System

    Science.gov (United States)

    Johnson, Aimee; Scott, Ryan; Ronca, April E.; Hoban-Higgins, Tana M.; Fuller, Charles A.; Alwood, Joshua S.

    2017-01-01

    During weightlessness, the skeletal system of astronauts is negatively affected by decreased calcium absorption and bone mass loss. Therefore, it is necessary to counteract these changes for long-term skeletal health during space flights. Our long-term plan is to assess artificial gravity (AG) as a possible solution to mitigate these changes. In this study, we aim to determine the skeletal acclimation to chronic centrifugation. We hypothesize that a 2G hypergravity environment causes an anabolic response in growing male rats. Specifically, we predict chronic 2G to increase tissue mineral density, bone volume fraction of the cancellous tissue and to increase overall bone strength. Systemically, we predict that bone formation markers (i.e., osteocalcin) are elevated and resorption markers (i.e., tartrate resistant acid phosphatase) are decreased or unchanged from controls. The experiment has three groups, each with an n8: chronic 2g, cage control (housed on the centrifuge, but not spun), and a vivarium control (normal rat caging). Pre-pubescent, male Long-Evans rats were used to assess our hypothesis. This group was subject to 90 days of 2G via centrifugation performed at the Chronic Acceleration Research Unit (CARU) at University of California Davis. After 90 days, animals were euthanized and tissues collected. Blood was drawn via cardiac puncture and the right leg collected for structural (via microcomputed tomography) and strength quantification. Understanding how counteract these skeletal changes will have major impacts for both the space-faring astronauts and the people living on Earth.

  1. Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats

    Directory of Open Access Journals (Sweden)

    Tian Ya-ping

    2010-07-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD, which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms. Results High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin, which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways. Conclusions Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.

  2. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    International Nuclear Information System (INIS)

    Guizar-Sahagun, G.; Rivera, F.; Babinski, E.; Berlanga, E.; Madrazo, M.; Franco-Bourland, R.; Grijalva, I.; Gonzalez, J.; Contreras, B.; Madrazo, I.

    1994-01-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  3. [Effect of puerarin in myocardial protection in rats with acute and chronic alcoholism].

    Science.gov (United States)

    Cui, Shu-qin

    2011-12-01

    To investigate the protective effect of puerarin on the myocardium of rats with acute and chronic alcoholism. In acute alcoholism experiment, normal male SD rats were randomly divided into the control group, alcoholism group and puerarin group (n=8), and high- and low-dose puerarin was administered. In chronic alcoholism experiment, increasing puerarin doses were given. Serum and myocardial levels of spartate aminotransferase (AST) and creatine phosphokinase (CPK) were determined using enzymatic methed, and superoxide dismutase (SOD), malondialdehyde (MDA), Ca(2+)-Mg(2+)-ATPase, and Na(+)-K(+)-ATPase in the myocardium were assayed with colorimetric method. HE staining was used to observe the microscopic changes of the myocardium. Compared with alcoholism group, puerarin-treated groups showed significantly lowered myocardial contents of MDA, CPK and AST and serum levels of AST and CPK (P0.05). HE staining of the myocardium showed cell swelling and obscure cell boundaries in alcoholism group, especially in chronic alcoholism group. The myocardial structure in puerarin group remained clear and regular. Puerarin can protect from myocardial injuries induced by acute and chronic alcoholism in rats.

  4. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guizar-Sahagun, G [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico); Rivera, F [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Babinski, E [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Berlanga, E [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Madrazo, M [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Franco-Bourland, R [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico); Grijalva, I [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

    1994-08-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  5. Sex-specific respiratory effects of acute and chronic caffeine administration in newborn rats.

    Science.gov (United States)

    Kouchi, Hayet; Uppari, NagaPraveena; Joseph, Vincent; Bairam, Aida

    2017-06-01

    Caffeine is widely used for the treatment of apnea of prematurity (AoP) but whether this effect varies with sex is unknown. To shed some light on this question, we present a summary of data obtained on the effects of caffeine on the respiratory chemoreflexes and apnea frequency in 1- and 12-days old male and female rats. Caffeine was either administered as a single acute injection (10mg/kg, i.p.) or for 10 consecutive days (7.5mg/kg/day between 3 and 12days of life by gavage, simulating its clinical use). Acute caffeine had little effects on breathing in 1-day old male and female rats. In 12-days old female rats caffeine reduced the response to hypercapnia (not hypoxia) compared to males. During the steady state of hypoxia females had a lower frequency of apneas than males, and acute injection of caffeine decreased the frequency of apnea, suppressing the differences between males and females. In 12-days old rats chronic administration of caffeine stimulated basal breathing and decreased the frequency of apnea similarly in males and females. In response to hypoxia, chronic caffeine administration also masked the difference in respiratory frequency between males and females observed in control rats. Female rats had lower frequency of apnea than males with or without caffeine treatment. These observations indicate that sex influences the respiratory responses to caffeine and this effect seems to depend on the modality of administration (acute vs chronic) and environmental oxygen (normoxia vs hypoxia). Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    mild stress and chronic escitalopram treatment. Furthermore, we investigated which classes of immature granule cells are affected by stress and targeted by escitalopram. Rats were initially exposed to 2weeks of CMS and 4weeks of escitalopram treatment with concurrent exposure to stress. The behavioral...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment......, but not in the rats that did not respond to escitalopram treatment. These changes were not followed by alterations in the volume of the granule cell layer. We also showed a differential regulation of dentate neurons, in different stages of development, by chronic stress and chronic escitalopram treatment. Our study...

  7. Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model.

    Science.gov (United States)

    Wei, Qin; Bian, Yeping; Yu, Fuchao; Zhang, Qiang; Zhang, Guanghao; Li, Yang; Song, Songsong; Ren, Xiaomei; Tong, Jiayi

    2016-11-01

    Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis. © 2016 by the Journal of Biomedical Research. All rights reserved.

  8. Protective action of tetramethylpyrazine on the medulla oblongata in rats with chronic hypoxia.

    Science.gov (United States)

    Ding, Yan; Hou, Xuefei; Chen, Li; Li, Hui; Tang, Yuhong; Zhou, Hua; Zhao, Shu; Zheng, Yu

    2013-01-01

    Tetramethylpyrazine (TMP), one of the active ingredients of the Chinese herb Lingusticum Wallichii Frantchat (Chuan Xiong), plays an important role in neuroprotection. However, the protective effect of TMP on the medulla oblongata, the most important region of the brain for cardiovascular and respiratory control, during chronic hypoxia remains unclear. In this study, we examined the neuroprotective effect of TMP on the medulla oblongata after chronic hypoxic injury in rats. Male Sprague-Dawley rats were randomly divided into four groups: control group, TMP group, chronic hypoxia group, and chronic hypoxia+TMP group. Rats were exposed to hypoxia (10% (v/v) O₂) or normoxia for 6 h daily for 14 days. TMP (80 mg/kg) or vehicle (saline) was injected intraperitoneally 30 min before experimentation. Loss of neurons in the pre-Bötzinger complex, the nucleus ambiguus, the nucleus tractus solitarius, the hypoglossal nucleus and the facial nucleus were evaluated by Nissl staining. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and apoptosis was monitored using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. The level of Bcl-2 mRNA and Bax mRNA was quantitatively measured by RT-PCR analysis. TMP protected Nissl bodies of neurons from injury in all nuclei observed, and reduced the loss of neurons in the nucleus ambiguus, the nucleus tractus solitarius, and the hypoglossal nucleus in rats subjected to chronic hypoxia. TMP upregulated SOD activity and inhibited the increase in MDA content in the medulla oblongata of hypoxic rats. In addition, TMP decreased the rate of apoptosis index (the percentage of apoptotic cells against the total number of cells) in all medullary structures examined, excepting the nucleus ambiguus and inhibited the decrease in Bcl-2 mRNA levels in the medulla oblongata following hypoxia. Our findings indicate that TMP may protect the medullary structures that are involved in

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

    International Nuclear Information System (INIS)

    Ammari, Mohamed; Brillaud, Elsa; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; Seze, Rene de; Faculte des Sciences de Bizerte, Jarzouna

    2008-01-01

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

  10. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress.

    Science.gov (United States)

    Rowson, Sydney A; Harrell, Constance S; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J; Kelly, Sean D; Reddy, Renuka; Neigh, Gretchen N

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  11. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

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    Godwin Sokpor

    2012-05-01

    Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

  12. The effect of chronic ethanol on glutamate binding in human and rat brain

    International Nuclear Information System (INIS)

    Cummins, J.T.; Sack, M.; von Hungen, K.

    1990-01-01

    Quantitative autoradiographic techniques demonstrate that chronic alcohol administration causes a decrease in [ 3 H]-glutamate binding to hippocampal N-methyl-D-aspartate (NMDA) receptors. A 14% decrease in [ 3 H]-glutamate binding in the hippocampal CA 1 region is seen both in the rat after five days of ethanol administration and in postmortem hippocampal tissues from alcoholics. In the rat, 24 hr ethanol withdrawal values are intermediate between control and alcohol binding levels. There was no significant effect of ethanol on [ 3 H]-glutamate binding in the cortex or caudate

  13. Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats

    International Nuclear Information System (INIS)

    Neisewander, J.L.; Lucki, I.; McGonigle, P.

    1991-01-01

    Alterations in the density of dopamine receptor subtypes and behaviors mediated by the D1-selective agonist SKF-38393 were examined in rats treated chronically with reserpine, SKF-38393 or the combination of these drugs. Animals received either vehicle or reserpine (1 mg/kg s.c.) on days 1 to 28 and, in addition, half of each of these groups were treated with vehicle and half were treated with SKF-38393 (5-10 mg/kg s.c.) on days 15 to 29. Quantitative autoradiographic measurement of D1 receptors labeled with [ 3 H]SCH-23390 and D2 receptors labeled with [ 3 H]spiroperidol revealed that chronic administration of reserpine increased the density of both receptor subtypes in the nucleus accumbens and caudate-putamen, but not in the substantia nigra. Chronic administration of SKF-38393 alone did not alter D1 receptor density in any of these regions. However, chronic administration of the agonist in reserpinized animals decreased D1 receptor density in the nucleus accumbens, but not in the caudate-putamen or substantia nigra, demonstrating that this partial agonist can selectively down-regulate D1 receptors when endogenous dopaminergic tone is removed. The chronic drug treatments also altered behavioral responses. Chronic administration of SKF-38393 alone produced sensitization of the oral dyskinesia response elicited by a challenge injection of the agonist, but no significant change in the grooming response. Acute administration of SKF-38393 in rats treated with reserpine for 14 days produced stereotypy which was not altered after chronic administration of the agonist. Surprisingly, chronic administration of reserpine alone produced a spontaneous oral dyskinesia, which was blocked dose-dependently by the D2-selective antagonist spiroperidol. These findings are discussed in terms of their relevance to Parkinson's disease and tardive dyskinesia

  14. Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.

    Science.gov (United States)

    Rayner, V C; Robinson, I C; Russell, J A

    1988-02-01

    1. Acutely, opioids inhibit oxytocin secretion. To study the responses of oxytocin neurones during chronic opioid exposure, forty-five lactating rats were infused continuously from a subcutaneous osmotically driven mini-pump via a lateral cerebral ventricle with morphine sulphate solution from day 2 post-partum for 5-7 days; the infusion rate was increased 2- or 2.5-fold each 40 h from 10 micrograms/h initially up to 50 micrograms/h; controls were infused with vehicle (1 microliter/h, twenty-eight rats) or were untreated (eight rats). 2. Maternal behaviour was disrupted in 27% of the morphine-treated rats; in rats that remained maternal morphine did not affect body weight or water intake but increased rectal temperature by 0.82 +/- 0.14 degrees C (mean +/- S.E.M.) across the first 4 days. 3. Weight gain of the litters of maternal morphine-treated rats was reduced by 32% during 7 days, predominantly in the first day of treatment when milk transfer was also reduced. Observation of pup behaviour during suckling showed decreased frequency of milk ejections on only the second day of morphine treatment. Plasma concentration of prolactin after 6 days was similar in maternal morphine-treated and control rats, but reduced by 90% in non-maternal morphine-treated rats, indicating normal control of prolactin secretion by suckling in morphine-treated rats. 4. Oxytocin and vasopressin contents, measured by radioimmunoassay, in the supraoptic and paraventricular nuclei and in the neurohypophysis were similar between fourteen maternal morphine-treated, twelve vehicle-treated and eight untreated lactating rats; thus exposure to morphine did not involve increased production and storage of oxytocin. 5. Distribution of [3H]morphine infused intracerebroventricularly into six virgin female rats for 6 days was measured by scintillation counting of tissue extracts. Morphine concentration in the hypothalamus and neurohypophysis was 2.7 and 12.8 micrograms/g, respectively, and in blood

  15. Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

    Science.gov (United States)

    Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

    2018-03-01

    Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall

  16. Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.

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    Li He

    Full Text Available It is well known that the mu-opioid receptor (MOR plays an important role in the rewarding properties of ethanol. However, it is less clear how chronic ethanol consumption affects MOR signaling. Here, we demonstrate that rats with prolonged voluntary ethanol consumption develop antinociceptive tolerance to opioids. Signaling through the MOR is controlled at many levels, including via the process of endocytosis. Importantly, agonists at the MOR that promote receptor endocytosis, such as the endogenous peptides enkephalin and β-endorphin, show a reduced propensity to promote antinociceptive tolerance than do agonists, like morphine, which do not promote receptor endocytosis. These observations led us to examine whether chronic ethanol consumption produced opioid tolerance by interfering with MOR endocytosis. Indeed, here we show that chronic ethanol consumption inhibits the endocytosis of MOR in response to opioid peptide. This loss of endocytosis was accompanied by a dramatic decrease in G protein coupled receptor kinase 2 (GRK2 protein levels after chronic drinking, suggesting that loss of this component of the trafficking machinery could be a mechanism by which endocytosis is lost. We also found that MOR coupling to G-protein was decreased in ethanol-drinking rats, providing a functional explanation for loss of opioid antinociception. Together, these results suggest that chronic ethanol drinking alters the ability of MOR to endocytose in response to opioid peptides, and consequently, promotes tolerance to the effects of opioids.

  17. Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

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    Popović Nataša

    2010-01-01

    Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

  18. Neurochemical Effects of Chronic Administration of Calcitriol in Rats

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    Pei Jiang

    2014-12-01

    Full Text Available Despite accumulating data showing the various neurological actions of vitamin D (VD, its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D administration (50 ng/kg/day or 100 ng/kg/day. Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH and tryptophan hydroxylase 2 (TPH2 expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.

  19. Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Battaini, F.; Govoni, S.; Rius, R.A.; Spano, P.F.; Trabucchi, M.

    1984-06-01

    Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.

  20. Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Battaini, F; Govoni, S; Rius, R A; Spano, P F; Trabucchi, M

    1984-06-01

    Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.

  1. Distinct effects of acute and chronic sleep loss on DNA damage in rats.

    Science.gov (United States)

    Andersen, M L; Ribeiro, D A; Bergamaschi, C T; Alvarenga, T A; Silva, A; Zager, A; Campos, R R; Tufik, S

    2009-04-30

    The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.

  2. Suyusan's effect on cytokine in the chronic mild unpredictable stressors depression rats

    International Nuclear Information System (INIS)

    Chen Liping; Wang Fawei; Lin Mingxiong; Dong Xiaojun; Zhang Yuanyuan

    2008-01-01

    To explore the serum levels of interleukin 2 (IL-2), interleukin 6 (IL-6) and tumor necrosis factor a (TNF-α) on chronic stress depression rat model treated with traditional chinese herbs. 40 wistar rats were randomly allocated to 5 groups as follows: control group, depression model group, lower dosage Suyusan group, higher dosage Suyusan group and amitriptyline group. Each group had 8 rats. Each rat was raised in one cage except the control group, in which 4 rats were raised in one cage. The levels of serum IL-2, IL-6 and TNF-α were observed by radioimmunoassay. The results showed that compared with control group, the serum IL-2, IL-6 and TNF-α levels in depression model group increased significantly (P<0.05); the serum IL-2, IL-6 levels in Suyusan group and amitriptyline group decreased, which had significant difference compared with those in depression model group (P<0.05). There was no significant difference between treatment group and control group. Conclusion: Suyusan decoction may regulate cytokine in the stressors induced depression rats, and maybe useful in depression treatment by decreasing cytokine which is high. (authors)

  3. Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

    Science.gov (United States)

    Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

    2013-04-01

    To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

  4. Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress

    Science.gov (United States)

    Wei, Sheng; Ji, Xiao-wei; Wu, Chun-ling; Li, Zi-fa; Sun, Peng; Wang, Jie-qiong; Zhao, Qi-tao; Gao, Jie; Guo, Ying-hui; Sun, Shi-guang; Qiao, Ming-qi

    2014-01-01

    Background Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. Material/Methods Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. Results In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. Conclusions Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS. PMID:24911067

  5. Lipid metabolism in rat tissues exposed to the chronic effects of γ-irradiation and ubiquinone Q9

    International Nuclear Information System (INIS)

    Novoselova, E.G.

    1992-01-01

    Chronic γ-irradiation of rats with the daily dose of 0.129 Gy activates the synthesis of various classes of lipids in the thymus, spleen and bone marrow cells and induces lipid accumulation in these tissues. Feeding of rats with the antioxidant, ubiquinone Q-9, under conditions of chronic irradiation causes a considerable normalization of lipogenesis and levels of the lipid concentration in the tissues of animals irradiated with the dose of 20 Gy

  6. Conditioned flavor avoidance as a measure of withdrawal in rats chronically exposed to a caffeine solution.

    Science.gov (United States)

    Dreumont-Boudreau, Sarah E; Dingle, Rachel N; Alcolado, Gillian M; Lolordo, Vincent M

    2008-09-03

    Rats were given 21 days of chronic oral caffeine. A novel flavor (Maintenance CS) was then paired with the continuation of caffeine, and a second flavor (Withdrawal CS) was paired with caffeine removal. Rats avoided the Withdrawal CS, and drank more of the Maintenance CS in a two-bottle test, suggesting that removing caffeine had induced withdrawal. The value of the Maintenance CS was investigated by comparing it to a novel flavor paired with water (Neutral CS). In a series of two-bottle tests, the Maintenance and Neutral CSs were equivalent when pitted against each other, and both were preferred to the Withdrawal CS. These results demonstrate that conditioned flavor avoidance is a useful procedure in assessing caffeine withdrawal, and by inference dependence, produced by chronic oral consumption.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  8. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2017-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  9. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2018-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  10. Effects of chronic administration of caffeine and stress on feeding behavior of rats.

    Science.gov (United States)

    Pettenuzzo, Leticia Ferreira; Noschang, Cristie; von Pozzer Toigo, Eduardo; Fachin, Andrelisa; Vendite, Deusa; Dalmaz, Carla

    2008-10-20

    Anorectic effects of caffeine are controversial in the literature, while stress and obesity are growing problems in our society. Since many stressed people are coffee drinkers, the objective of the present study was to evaluate the effect of stress and chronic administration of caffeine on feeding behavior and body weight in male and female rats. Wistar rats (both males and females) were divided into 3 groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated-restraint stress for 40 days). During the entire treatment, chow consumption was monitored and rats were weighed monthly. Afterwards, feeding behavior was evaluated during 3-min trials in food-deprived and ad libitum fed animals and also in repeated exposures, using palatable food (Froot Loops and Cheetos). Chronic administration of caffeine did not affect rat chow consumption or body weight gain, but diminished the consumption of both salty (Cheetos) and sweet (Froot Loops) palatable food. In the repeated trial tests, stress diminished savory snack consumption in the later exposures [I.S. Racotta, J. Leblanc, D. Richard The effect of caffeine on food intake in rats: involvement of corticotropin-releasing factor and the sympatho-adrenal system. Pharmacol Biochem Behav. 1994, 48:887-892; S.D. Comer, M. Haney, R.W. Foltin, M.W. Fischman Effects of caffeine withdrawal on humans living in a residential laboratory. Exp Clin Psychopharmacol. 1997, 5:399-403; A. Jessen, B. Buemann, S. Toubro, I.M. Skovgaard, A. Astrup The appetite-suppressant effect of nicotine is enhanced by caffeine. Diab Ob Metab. 2005, 7:327-333; J.M. Carney Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. Br J Pharmacol. 1982, 75:451-454] and caffeine diminished consumption of both palatable foods (savory and sweet) during the early and later exposures. Most responses to caffeine were stronger

  11. Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats

    Directory of Open Access Journals (Sweden)

    Jae-Heung Park

    2015-03-01

    Full Text Available Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘 and ST36 (足三里 were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX, B-cell lymphoma 2 (Bcl-2 and Transforming growth factor-beta 1 (TGF-β1. Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

  12. Sweet food improves chronic stress-induced irritable bowel syndrome-like symptoms in rats.

    Science.gov (United States)

    Rho, Sang-Gyun; Kim, Yong Sung; Choi, Suck Chei; Lee, Moon Young

    2014-03-07

    To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines. Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis. In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.

  13. [Effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea].

    Science.gov (United States)

    Huang, Zu-xiong; Ye, Li-yan; Zheng, Zhi-yong; Chen, Xin-min; Ren, Rong-na; Tong, Guo-yuan

    2005-05-01

    To investigate the nutrient effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea. Forty 21-day-old wistar rats were randomly divided into five groups (8 in each). Animal model of chronic diarrhea was induced by a lactose enriched diet in the weanling Wistar rat, normal control group was fed with a standard semipurified diet, and after 14 days the rats in both groups were killed to test the establishment of the model. After the establishment of the model, the other groups were fed with the standard semipurified diet to recover for 7 days, and were randomly divided into three groups: non-intervention group, glutamine (Gln)-intervention group and control group. Glutamine concentrations in blood was detected by high-performance liquid chromatography (HPLC). Morphological changes including villus height and villus surface area of the jejunum were measured under a light microscope and electron microscope, expression of proliferating cell nuclear antigen (PCNA) as an index of cell proliferation was observed using immunohistochemical staining and image analysis. The diarrhea rate in model group was 100 percent, average diarrhea index was 1.16 +/- 0.06, but both diarrhea rate and average diarrhea index in control group were 0 (P body weight, plasma Gln concentration, villus height, villus surface area and expression of PCNA in non-intervened group compared with the control group (P body weight, villus height and villus surface area in Gln-intervened group compared with control group (P 0.05). And compared with non-intervened group, except for body weight (P > 0.05), plasma glutamine, villus height, villus surface area and expression of PCNA were all significantly increased in Gln-intervened group. Chronic diarrhea can induce malnutrition and reduce the villus height, villus surface area, expression of PCNA and plasm glutamine concentration. Oral glutamine could improve the proliferation of crypt cell and promote repair of intestinal mucosa

  14. Effect of long-term chronic irradiation on gluconeogenesis in rats

    International Nuclear Information System (INIS)

    Paulikova, E.; Ahlers, I.; Praslicka, M.

    1982-01-01

    The incorporation of 14 C-acetate in glucose in the blood and in glycogen in the liver of rats chronically irradiated with gamma radiation was observed in vivo. During the period of observation the concentration of glycogen in the liver was increased. Increased acetate incorporation in glycogen was, however, observed only on day 30 of exposure. No changes in glucose concentration and acetate incorporation in glucose in the blood were observed. (M.D.)

  15. Mechanisms Mediating Vibration-induced Chronic Musculoskeletal Pain Analyzed in the Rat

    OpenAIRE

    Dina, Olayinka A.; Joseph, Elizabeth K.; Levine, Jon D.; Green, Paul G.

    2009-01-01

    While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60–80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia t...

  16. Immune homeostasis disturbances in different generations of rats at chronic exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Mel'nikov, O.F.; Sambur, M.B.; Timchenko, S.V.; Rozenfel'd, L.G.; Yindik, V.M.; Zayats, T.A.

    1994-01-01

    The aim of the work was to study immune homeostasis disturbance in six generations of rats which were kept under the conditions of chronic exposure to small doses of low-intensity radiation resembling those after the accident at Chernobyl Atomic Power Station. The controls included the animals from Kiev vivarium. Leukopenia and lymphopenia of different stage, decrease of the absolute number of immunocompetent cell having Fc receptor to lg G, inhibition of their functional activity, increase of mastocytelike lymphocytes in the peripheral blood, stable suppression of natural cytotoxic cells activity has been found out in the rats of the experimental groups examined at the age 3, 6, 9 and 12 months. The revealed disturbances of cell immunity indices and nonspecific resistance factors depended on the age of the animals and their generation to greater extend in the young rats of F 1 -F 2 generation

  17. Rat behaviour reactions and brain synaptic membrane lipids under the chronical gamma-irradiation

    International Nuclear Information System (INIS)

    Semenova, T.P.; Medvinskaya, N.I.; Potekhina, N.I.; Kolomijtseva, I.K.

    1997-01-01

    The effects of low level chronical ionising irradiation (12.9 cGy/day on the sensory attention to the stimuli of different modalities (somatosensor, visual, odor) of Wistar rats were studied. Analysis of animals behaviour was made after they had received the different doses of irradiation: 4, 6, 8, 10, 15 and 20 Gy. It was founded, that the attention and exploratory activity of rats is significantly decreased up to 20-30% after 4-6 Gy. The irradiation doses 8 Gy did not change animal behaviour as compared to control animals, but doses 10, 15 and 20 Gy decreased the exploratory activity as well as sensory attention of rats to 3-5-times as compared to previous dose. Such a wave-like way of behaviour reflects the functioning of an adaptive mechanism. Biochemical data indicated that after 5 months of the irradiation (dose 20 Gy) the level of phospholipids, lysophosphatidylcholine, phosphatdylethanolamine, phosphatidylcholine, cholesterol were decreased

  18. Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.

    Directory of Open Access Journals (Sweden)

    Douglas Carvalho Caixeta

    Full Text Available Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.

  19. Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons.

    Science.gov (United States)

    Yong, V W; Perry, T L; Godolphin, W J; Jones, K A; Clavier, R M; Ito, M; Foulks, J G

    1986-01-01

    In an attempt to produce an animal model of Parkinson's disease, we injected rats repeatedly with high doses of methylcyclopentadienyl manganese tricarbonyl (MMT), a compound which has been reported to lower striatal dopamine content in mice. Chronic MMT administration for up to 5 months, even though it produced a substantial elevation in brain manganese content during the period of exposure, did not destroy dopaminergic nigrostriatal neurons. This was assessed by measurements of tyrosine hydroxylase activity and contents of dopamine and its metabolites in the striatum, and by histological examination of the substantia nigra. Our results differ from those of others who administered manganese chloride in drinking water to rats. This discrepancy is unlikely to be a consequence of differences in duration of exposure or route of administration. It could be due to our having used an organic rather than an inorganic manganese compound, or to a species difference in vulnerability to organic manganese between rats and mice.

  20. Chronic leptin infusion advances, and immunoneutralization of leptin postpones puberty onset in normally fed and feed restricted female rats

    NARCIS (Netherlands)

    Zeinoaldini, S.; Swarts, J.J.M.; Heijning, van de B.J.M.

    2006-01-01

    Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14 days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset

  1. Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning.

    Science.gov (United States)

    Cevik, Ozge Selin; Sahin, Leyla; Tamer, Lulufer

    2018-05-01

    The type and duration of exposure to stress is an important influence on emotional and cognitive functions. Learning is the adaptive response of the central nervous system that occurs in hippocampus which affects from environmental factors like exercise. In this study, we investigated effects of long term treadmill exercise on learning and behavior on chronic social isolated rat. Male Wistar rats (n = 32) randomly assigned into four groups: control, exercised, social isolation, social isolation + exercise during postnatal days (PNDs) 21-34. Social isolation protocol was applied during 14 days by placing rat in a cage one by one. Rats were exercised during 5 days, days were chosen randomly for overall 4 weeks (20, 30, 50, 60 min respectively). Finally, learning performance was evaluated by Morris water maze (MWM). Anxiety behavior was evaluated by Open field and elevated plus maze test. At the end of learning and behavior tests, the rats were decapitated to collect blood samples via intracardiac puncture and corticosterone analysis was performed with ELISA method. Animal weights and water consumption did not change significantly but food intake differed among groups. Corticosterone level did not change between groups. The frequency of entering to the target quadrant increased in exercised rat significantly. However, there was no difference in learning and memory in rats. Treadmill exercise reduced anxiety behavior significantly. Taken together these findings may point out that, long term treadmill exercise did not change learning and memory but reduced anxiety level of rat without changing corticosterone level. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

    Science.gov (United States)

    Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

    2017-03-01

    Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats

    Institute of Scientific and Technical Information of China (English)

    潘宝龙

    2013-01-01

    Objective To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in SpragueDawley (SD) rats.Methods Thirty-two male SD rats were randomly and equally divided into 4 groups:control group and high-,middle-,and low-dose exposure groups.The rats in high-,middle-,and low-dose expo-

  4. Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

    Science.gov (United States)

    Miranda, J; Lamana, S M S; Dias, E V; Athie, M; Parada, C A; Tambeli, C H

    2015-02-12

    We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain. Copyright © 2014 IBRO

  5. Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure.

    Science.gov (United States)

    Rouas, Caroline; Souidi, Maâmar; Grandcolas, Line; Grison, Stephane; Baudelin, Cedric; Gourmelon, Patrick; Pallardy, Marc; Gueguen, Yann

    2009-11-01

    The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment. Copyright © 2009 Elsevier B.V. All rights reserved.

  6. Role of insular cortex in visceral hypersensitivity model in rats subjected to chronic stress.

    Science.gov (United States)

    Yi, LiSha; Sun, HuiHui; Ge, Chao; Chen, Ying; Peng, HaiXia; Jiang, YuanXi; Wu, Ping; Tang, YinHan; Meng, QingWei; Xu, ShuChang

    2014-12-30

    Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.

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

    Directory of Open Access Journals (Sweden)

    Namdar Yousofvand

    2015-09-01

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

  8. Acute and chronic stress and the inflammatory response in hyperprolactinemic rats.

    Science.gov (United States)

    Ochoa-Amaya, J E; Malucelli, B E; Cruz-Casallas, P E; Nasello, A G; Felicio, L F; Carvalho-Freitas, M I R

    2010-01-01

    Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period. Copyright 2010 S. Karger AG, Basel.

  9. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

    Science.gov (United States)

    Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest

    2013-10-01

    There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

    Science.gov (United States)

    Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

    2016-09-01

    Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

  11. Decrease in Circulating Fatty Acids Is Associated with Islet Dysfunction in Chronically Sleep-Restricted Rats

    Directory of Open Access Journals (Sweden)

    Shanshan Zhan

    2016-12-01

    Full Text Available Previous studies have shown that sleep restriction-induced environmental stress is associated with abnormal metabolism, but the underlying mechanism is poorly understood. In the current study, we investigated the possible lipid and glucose metabolism patterns in chronically sleep-restricted rat. Without changes in food intake, body weight was decreased and energy expenditure was increased in sleep-restricted rats. The effects of chronic sleep disturbance on metabolites in serum were examined using 1H NMR metabolomics and GC-FID/MS analysis. Six metabolites (lipoproteins, triglycerides, isoleucine, valine, choline, and phosphorylcholine exhibited significant alteration, and all the fatty acid components were decreased, which suggested fatty acid metabolism was impaired after sleep loss. Moreover, increased blood glucose, reduced serum insulin, decreased glucose tolerance, and impaired glucose-stimulated insulin secretion of islets were also observed in sleep-restricted rats. The islet function of insulin secretion could be partially restored by increasing dietary fat to sleep-disturbed rats suggested that a reduction in circulating fatty acids was related to islet dysfunction under sleep deficiency-induced environmental stress. This study provides a new perspective on the relationship between insufficient sleep and lipid/glucose metabolism, which offers insights into the role of stressful challenges in a healthy lifestyle.

  12. Central and peripheral effects of chronic food restriction and weight restoration in the rat.

    Science.gov (United States)

    Kinzig, Kimberly P; Hargrave, Sara L; Tao, Erin E

    2009-02-01

    Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

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

    Directory of Open Access Journals (Sweden)

    MA Khalili

    2004-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Chronic stress effects and their reversibility on the Fallopian tubes and uterus in rats.

    Science.gov (United States)

    Divyashree, S; Yajurvedi, H N

    2018-01-01

    The durational effects of chronic stress on the Fallopian tubes and uterus were studied by exposing rats to stressors in the form of restraint (1h) and forced swimming (15min) daily for 4, 8 or 12 weeks. One group of stressed rats from each time period was then maintained without exposure to stressors for a further 4 weeks to assess their ability to recover from stress. All time periods of stress exposure resulted in decreased weight of the body and Fallopian tubes; however, the relative weight of the uterus and serum concentrations of oestradiol and insulin increased significantly. The antioxidant potential was decreased with increased malondialdehyde concentrations in the Fallopian tubes following all durations of exposure and after 4 and 8 weeks of stress exposure in the uterus. Interestingly, rats stressed for 12 weeks showed an increase in serum testosterone concentration and antioxidant enzyme activities with a decrease in malondialdehyde concentration in the uterus. The antioxidant enzyme activities and malondialdehyde concentration in the Fallopian tubes of all recovery group rats were similar to stressed rats. However, in the uterus these parameters were similar to controls in recovery group rats after 4 weeks or 8 weeks of exposure, but after 12 weeks of stress exposure these parameters did not return to control levels following the recovery period. These results reveal, for the first time, that chronic stress elicits an irreversible decrease in antioxidant defence in the Fallopian tubes irrespective of exposure duration, whereas the uterus develops reversible oxidative stress under short-term exposure but increased antioxidant potential with endometrial proliferation following long-term exposure.

  16. Two chronic motor training paradigms differentially influe nce acute instrume ntal learning in spinally transected rats

    Science.gov (United States)

    Bigbee, Allison J.; Crown, Eric D.; Ferguson, Adam R.; Roy, Roland R.; Tillakaratne, Niranjala J.K.; Grau, James W.; Edgerton, V. Reggie

    2008-01-01

    The effect of two chronic motor training paradigms on the ability of the lumbar spinal cord to perform an acute instrumental learning task was examined in neonatally (postnatal day 5; P5) spinal cord transected (i.e., spinal) rats. At ∼P30, rats began either unipedal hindlimb stand training (Stand-Tr; 20-25 min/day, 5 days/wk), or bipedal hindlimb step training (Step-Tr; 20 min/day; 5 days/wk) for 7 wks. Non-trained spinal rats (Non-Tr) served as controls. After 7 wks all groups were tested on the flexor-biased instrumental learning paradigm. We hypothesized that 1) Step-Tr rats would exhibit an increased capacity to learn the flexor-biased task relative to Non-Tr subjects, as locomotion involves repetitive training of the tibialis anterior (TA), the ankle flexor whose activation is important for successful instrumental learning, and 2) Stand-Tr rats would exhibit a deficit in acute motor learning, as unipedal training activates the ipsilateral ankle extensors, but not flexors. Results showed no differences in acute learning potential between Non-Tr and Step-Tr rats, while the Stand-Tr group showed a reduced capacity to learn the acute task. Further investigation of the Stand-Tr group showed that, while both the ipsilateral and contralateral hindlimbs were significantly impaired in their acute learning potential, the contralateral, untrained hindlimbs exhibited significantly greater learning deficits. These results suggest that different types of chronic peripheral input may have a significant impact on the ability to learn a novel motor task, and demonstrate the potential for experience-dependent plasticity in the spinal cord in the absence of supraspinal connectivity. PMID:17434606

  17. Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats.

    Science.gov (United States)

    Masuda, Takahiro; Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

    2018-01-01

    Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). The aim of this study was to clarify the effect of LDA on chronic RE in rats. Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

  18. Brain energy metabolism is activated after acute and chronic administration of fenproporex in young rats.

    Science.gov (United States)

    Rezin, Gislaine T; Jeremias, Isabela C; Ferreira, Gabriela K; Cardoso, Mariane R; Morais, Meline O S; Gomes, Lara M; Martinello, Otaviana B; Valvassori, Samira S; Quevedo, João; Streck, Emilio L

    2011-12-01

    Obesity is a chronic disease of multiple etiologies, including genetic, metabolic, environmental, social, and other factors. Pharmaceutical strategies in the treatment of obesity include drugs that regulate food intake, thermo genesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine. Studies suggest that amphetamine induces neurotoxicity through generation of free radicals and mitochondrial apoptotic pathway by cytochrome c release, accompanied by a decrease of mitochondrial membrane potential. Mitochondria are intracellular organelles that play a crucial role in ATP production. Thus, in the present study we evaluated the activities of some enzymes of Krebs cycle, mitochondrial respiratory chain complexes and creatine kinase in the brain of young rats submitted to acute and chronic administration of fenproporex. In the acute administration, the animals received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or tween. In the chronic administration, the animals received a single injection daily for 14 days of fenproporex (6.25, 12.5 or 25 mg/Kg i.p.). Two hours after the last injection, the rats were sacrificed by decapitation and the brain was removed for evaluation of biochemical parameters. Our results showed that the activities of citrate synthase, malate dehydrogenase and succinate dehydrogenase were increased by acute and chronic administration of fenproporex. Complexes I, II, II-III and IV and creatine kinase activities were also increased after acute and chronic administration of the drug. Our results are consistent with others reports that showed that some psychostimulant drugs increased brain energy metabolism in young rats. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  19. Effect of chronic restraint stress on inhibitory gating in the auditory cortex of rats.

    Science.gov (United States)

    Ma, Lanlan; Li, Wai; Li, Sibin; Wang, Xuejiao; Qin, Ling

    2017-05-01

    A fundamental adaptive mechanism of auditory function is inhibitory gating (IG), which refers to the attenuation of neural responses to repeated sound stimuli. IG is drastically impaired in individuals with emotional and cognitive impairments (i.e. posttraumatic stress disorder). The objective of this study was to test whether chronic stress impairs the IG of the auditory cortex (AC). We used the standard two-tone stimulus paradigm and examined the parametric qualities of IG in the AC of rats by recording the electrophysiological signals of a single-unit and local field potential (LFP) simultaneously. The main results of this study were that most of the AC neurons showed a weaker response to the second tone than to the first tone, reflecting an IG of the repeated input. A fast negative wave of LFP showed consistent IG across the sampled AC sites, whereas a slow positive wave of LFP had less IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level, due to the increase in response to the second tone. This study provided new evidence that chronic stress disrupts the physiological function of the AC. Lay Summary The effects of chronic stress on IG were investigated by recording both, single-unit spike and LFP activities, in the AC of rats. In normal rats, most of the single-unit and N25 LFP activities in the AC showed an IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level.

  20. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    International Nuclear Information System (INIS)

    Hantson, Philippe; Grandin, Cecile; Duprez, Thierry; Nassogne, Marie-Cecile; Guerit, Jean-Michel

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 μmol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  1. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    Energy Technology Data Exchange (ETDEWEB)

    Hantson, Philippe [Universite Catholique de Louvain, Department of Intensive Care, Cliniques Saint-Luc, Brussels (Belgium); Grandin, Cecile; Duprez, Thierry [Universite Catholique de Louvain, Department of Neuroradiology, Cliniques Saint-Luc, Brussels (Belgium); Nassogne, Marie-Cecile [Universite Catholique de Louvain, Department of Pediatric Neurology, Cliniques Saint-Luc, Brussels (Belgium); Guerit, Jean-Michel [Universite Catholique de Louvain, Laboratory of Neurophysiology, Cliniques Saint-Luc, Brussels (Belgium)

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 {mu}mol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  2. TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

    Directory of Open Access Journals (Sweden)

    Cheng-Bin Chen

    2010-08-01

    Full Text Available The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCGconsisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG 10 rats, and Uremic Clearance Granules Treatment Group (UCG 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGFbeta1 promoter was tested by methylation-specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1 Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05, improve renal function. (2 The expression of TGF-beta1 in mRNA and protein level were down-regulated. (3 TGF-beta1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

  3. Chronic lead intoxication affects glial and neural systems and induces hypoactivity in adult rat.

    Science.gov (United States)

    Sansar, Wafa; Ahboucha, Samir; Gamrani, Halima

    2011-10-01

    Lead is an environmental toxin and its effects are principally manifested in the brain. Glial and neuronal changes have been described during development following chronic or acute lead intoxication, however, little is known about the effects of chronic lead intoxication in adults. In this study we evaluated immunohistochemically the glial and dopaminergic systems in adult male Wistar rats. 0.5% (v/v) lead acetate in drinking water was administrated chronically over a 3-month period. Hypertrophic immunoreactive astrocytes were observed in the frontal cortex and other brain structures of the treated animals. Analysis of the astroglial features showed increased number of astrocyte cell bodies and processes in treated rats, an increase confirmed by Western blot. Particular distribution of glial fibrillary acidic protein immunoreactivity was observed within the blood vessel walls in which dense immunoreactive glial processes emanate from astrocytes. Glial changes in the frontal cortex were concomitant with reduced tyrosine hydroxylase immunoreactive neuronal processes, which seem to occur as a consequence of significantly reduced dopaminergic neurons within the nucleus of origin in the substantia nigra. These glial and neuronal changes following lead intoxication may affect animal behavior as evidenced by reduced locomotor activity in an open field test. These findings demonstrate that chronic lead exposure induces astroglial changes, which may compromise neuronal function and consequently animal behavior. Copyright © 2010 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

    BACKGROUND/OBJECTIVES Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS Chronic alcohol intake significantly increased serum tumor necrosis factor-α (TNF-α) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-α gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels. CONCLUSIONS The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system. PMID:26244074

  5. Proteomic analysis of urine in rats chronically exposed to fluoride.

    Science.gov (United States)

    Kobayashi, Claudia Ayumi Nakai; Leite, Aline de Lima; da Silva, Thelma Lopes; dos Santos, Lucilene Delazari; Nogueira, Fábio César Sousa; Santos, Keity Souza; de Oliveira, Rodrigo Cardoso; Palma, Mario Sérgio; Domont, Gilberto Barbosa; Buzalaf, Marília Afonso Rabelo

    2011-01-01

    Urine is an ideal source of materials to search for potential disease-related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2-DE-based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F(-)) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F(-) for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F(-) excretion. Urinary proteome profiles were examined using 2-DE and Colloidal Coomassie Brilliant Blue staining. A dose-response regarding F(-) intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F(-), control vs. 50 ppm F(-) and 5 ppm F(-) vs. 50 ppm F(-) groups, respectively. Two proteins regulated by androgens (androgen-regulated 20-KDa protein and α-2μ-globulin) and one related to detoxification (aflatoxin-B1-aldehyde-reductase) were identified by MALDI-TOF-TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F(-) toxicity, even in low doses. Copyright © 2010 Wiley Periodicals, Inc.

  6. Effect of superoxide anion scavenger on rat hearts with chronic intermittent hypoxia.

    Science.gov (United States)

    Pai, Peiying; Lai, Ching Jung; Lin, Ching-Yuang; Liou, Yi-Fan; Huang, Chih-Yang; Lee, Shin-Da

    2016-04-15

    Only very limited information regarding the protective effects of the superoxide anion scavenger on chronic intermittent hypoxia-induced cardiac apoptosis is available. The purpose of this study is to evaluate the effects of the superoxide anion scavenger on cardiac apoptotic and prosurvival pathways in rats with sleep apnea. Forty-two Sprague-Dawley rats were divided into three groups, rats with normoxic exposure (Control, 21% O2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide anion scavenger and chronic intermittent hypoxia exposure (Hypoxia-O2 (-)-Scavenger, MnTMPyP pentachloride, 1 mg/kg ip per day; 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo) at 5-6 mo of age. After 1 mo, the protein levels and apoptotic cells of excised hearts from three groups were measured by Western blotting and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. The superoxide anion scavenger decreased hypoxia-induced myocardial architecture abnormalities, left ventricular hypertrophy, and TUNEL-positive apoptosis. The superoxide anion scavenger decreased hypoxia-induced Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathway) as well as Bad, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptotic pathway), endonuclease G (EndoG), apoptosis-inducing factor (AIF), and TUNEL-positive apoptosis. The superoxide anion scavenger increased IGF-1, IGF-1R, p-PI3k, p-Akt, p-Bad, Bcl-2, and Bcl-xL (survival pathway). Our findings imply that the superoxide anion scavenger might prevent cardiac Fas-mediated and mitochondrial-mediated apoptosis and enhance the IGF-1-related survival pathway in chronic intermittent hypoxia. The superoxide anion scavenger may prevent chronic sleep apnea-enhanced cardiac apoptotic pathways and enhances

  7. Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper gastrointestinal hemorrhage or valproate side effect?: Case report and literature review.

    Science.gov (United States)

    Guo, Xiaopeng; Wei, Junji; Gao, Lu; Xing, Bing; Xu, Zhiqin

    2017-04-01

    Postoperative coma is not uncommon in patients after craniotomy. It generally presents as mental state changes and is usually caused by intracranial hematoma, brain edema, or swelling. Hyperammonemia can also result in postoperative coma; however, it is rarely recognized as a potential cause in coma patients. Hyperammonemic coma is determined through a complicated differential diagnosis, and although it can also be induced as a side effect of valproate (VPA), this cause is frequently unrecognized or confused with upper gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy. We herein present a case of valproate-induced hyperammonemic encephalopathy (VHE) to illustrate the rarity of such cases and emphasize the importance of correct diagnosis and proper treatment. A 61-year-old woman with meningioma was admitted into our hospital. Radical resection of the tumor was performed, and the patient recovered well as expected. After administration of valproate for 7 days, the patient was suddenly found in a deep coma, and her mental state deteriorated rapidly. The diagnoses of hepatic encephalopathy was confirmed. However, whether it origins from upper gastrointestinal hemorrhage or valproate side effect is uncertain. The patient's condition fluctuated without improvement during the subsequent 3 days under the treatment of reducing ammonia. With the discontinuation of valproate treatment, the patient regained complete consciousness within 48 hours, and her blood ammonia decreased to the normal range within 4 days. VHE is a rare but serious complication in patients after craniotomy and is diagnosed by mental state changes and elevated blood ammonia. Thus, the regular perioperative administration of VPA, which is frequently neglected as a cause of VHE, should be emphasized. In addition, excluding UGH prior to providing a diagnosis and immediately discontinuing VPA administration are recommended.

  8. Quantitative and qualitative changes in the lymphocytes of rats chronically exposed to radiation and chemical factors

    International Nuclear Information System (INIS)

    Ivanov, V.V.

    1986-01-01

    Quantitative and qualitative characteristics of lymphocytes in peripheral blood, thymus and spleen of rats chronically exposed to combined external γ-radiation trichlorfon pesticide effect have been studied. It is shown that chronical combined trichlorfon and γ irradiation effect is accompanied by suppression of lymphopoiesis already at the early stages of the experience. The observed effects are formed depending on both daily and cumulative doses of the effect. The development of the combined effect is based on the summation of effects of chronical effect of ionizing radiation and pesticide. The revealed changes in lymphocytes population exposed to radiation and chemical factors can lead to substantial decrease of natural immunity thereby decreasing to various diseases

  9. Increased Autolysis of μ-Calpain in Skeletal Muscles of Chronic Alcohol-Fed Rats.

    Science.gov (United States)

    Gritsyna, Yulia V; Salmov, Nikolay N; Bobylev, Alexander G; Ulanova, Anna D; Kukushkin, Nikolay I; Podlubnaya, Zoya A; Vikhlyantsev, Ivan M

    2017-10-01

    Proteolysis can proceed via several distinct pathways such as the lysosomal, calcium-dependent, and ubiquitin-proteasome-dependent pathways. Calpains are the main proteases that cleave a large variety of proteins, including the giant sarcomeric proteins, titin and nebulin. Chronic ethanol feeding for 6 weeks did not affect the activities of μ-calpain and m-calpain in the m. gastrocnemius. In our research, changes in μ-calpain activity were studied in the m. gastrocnemius and m. soleus of chronically alcohol-fed rats after 6 months of alcohol intake. SDS-PAGE analysis was applied to detect changes in titin and nebulin contents. Titin phosphorylation analysis was performed using the fluorescent dye Pro-Q Diamond. Western blotting was used to determine μ-calpain autolysis as well as μ-calpain and calpastatin contents. The titin and nebulin mRNA levels were assessed by real-time PCR. The amounts of the autolysed isoform (78 kDa) of full-length μ-calpain (80 kDa) increased in the m. gastrocnemius and m. soleus of alcohol-fed rats. The calpastatin content increased in m. gastrocnemius. Decreased intact titin-1 (T1) and increased T2-proteolytic fragment contents were found in the m. gastrocnemius and m. soleus of the alcohol-fed rats. The nebulin content decreased in the rat gastrocnemius muscle of the alcohol-fed group. The phosphorylation levels of T1 and T2 were increased in the m. gastrocnemius and m. soleus, and decreased titin and nebulin mRNA levels were observed in the m. gastrocnemius. The nebulin mRNA level was increased in the soleus muscle of the alcohol-fed rats. In summary, our data suggest that prolonged chronic alcohol consumption for 6 months resulted in increased autolysis of μ-calpain in rat skeletal muscles. These changes were accompanied by reduced titin and nebulin contents, titin hyperphosphorylation, and development of hindlimb muscle atrophy in the alcohol-fed rats. Copyright © 2017 by the Research Society on Alcoholism.

  10. The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

    Science.gov (United States)

    Reed, Adam H.; McCarty, Heidi L.; Evans, Glenda L.; Turner, Russell T.; Westerlind, Kim C.

    2002-01-01

    BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no

  11. Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

    2018-03-01

    Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensi s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.

  12. Major depressive disorder mediates accelerated aging in rats subjected to chronic mild stress.

    Science.gov (United States)

    Xie, Xiaoxian; Chen, Yangyang; Ma, Lingyan; Shen, Qichen; Huang, Liangfeng; Zhao, Binggong; Wu, Tao; Fu, Zhengwei

    2017-06-30

    Major depressive disorder (MDD) has a complex etiology and is characterized by a change in mood and psychophysiological state. MDD has been shown to mediate accelerated biological aging in patients, although the underlying mechanism is not well understood. In the present study, we used a chronic mild stress (CMS) paradigm to induce anhedonia, one of the main symptoms of MDD. CMS induced depression-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swim test. Moreover, stressed rats travelled a shorter total distance, had fewer grid line crossings, and spent less time in the outer zone in the open field test than controls. CMS altered the levels of 5-hydroxytryptophan, dopamine, and corticosterone in the serum and hippocampus (P<0.05); these rats also exhibited impaired liver function, decreased telomerase activity, and telomere shortening, which was associated with increased oxidative damage along with decreased superoxide dismutase and glutathione reductase activities. Mitochondria in CMS-treated rats showed ultrastructural damage as well as reduced DNA content and integrity. These findings provide physiological and cellular evidence that the MDD can mediate accelerated aging in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Chronic social instability increases anxiety-like behavior and ethanol preference in male Long Evans rats.

    Science.gov (United States)

    Roeckner, Alyssa R; Bowling, Alexandra; Butler, Tracy R

    2017-05-01

    Chronic stress during adolescence is related to increased prevalence of anxiety disorders and alcohol use disorders in humans. This phenotype has been consistently recapitulated in animal models with male subjects, but models using female subjects are fewer. The aim of these studies was to test the hypothesis that chronic social instability (CSI) during adolescence engenders increased anxiety-like behavior, increased corticosterone, and greater ethanol intake and/or preference than control groups in male and female rats. A chronic social instability (CSI) procedure was conducted in separate cohorts of female and male adolescent Long Evans rats. CSI included daily social isolation for 1h, and then pair housing with a novel cage mate for 23h until the next 1h isolation period from PND 30-46. Control groups included social stability (SS), chronic isolation (ISO), and acute social instability (aSI). At PND 49-50, anxiety-like behavior was assessed on the elevated plus maze, and on PND 51 tails bloods were obtained for determination of corticosterone (CORT) levels. This was followed by 4weeks of ethanol drinking in a home cage intermittent access ethanol drinking paradigm (PND 55-81 for males, PND 57-83 for females). Planned contrast testing showed that the male CSI group had greater anxiety-like behavior compared controls, but group differences were not apparent for CORT. CSI males had significantly higher levels of ethanol preference during drinking weeks 2-3 compared to all other groups and compared to SS and ISO groups in week 4. For the female cohort, we did not observe consistent group differences in anxiety-like behavior, CORT levels were unexpectedly lower in the ISO group only compared to the other groups, and group differences were not apparent for ethanol intake/preference. In conclusion, chronic stress during adolescence in the form of social instability increases anxiety-like behavior and ethanol preference in male rats, consistent with other models of

  14. Ventilatory and chemoreceptor responses to hypercapnia in neonatal rats chronically exposed to moderate hyperoxia.

    Science.gov (United States)

    Bavis, Ryan W; Li, Ke-Yong; DeAngelis, Kathryn J; March, Ryan J; Wallace, Josefine A; Logan, Sarah; Putnam, Robert W

    2017-03-01

    Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO 2 /pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O 2 (Control) or 60% O 2 (Hyperoxia) until studied at 4, 6-7, or 13-14days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO 2 at all ages; CO 2 sensitivity recovered within 7days after return to room air. Hypercapnic responses of CO 2 -sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO 2 were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Gueguen, Y.; Grandcolas, L.; Baudelin, C.; Grison, S.; Tissandie, E.; Jourdain, J.R.; Paquet, F.; Voisin, P.; Aigueperse, J.; Gourmelon, P.; Souidi, M.

    2007-01-01

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

  16. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

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    Massimo Collino

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1 induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO. These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO activity, interleukin 1β (IL-1β production and tumor necrosis factor-α (TNFα production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  17. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

    Science.gov (United States)

    Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  18. Effect of Inhaling Bergamot Oil on Depression-Related Behaviors in Chronic Stressed Rats.

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    Saiyudthong, Somrudee; Mekseepralard, Chantana

    2015-10-01

    Bergamot essential oil (BEO) possesses sedation and anxiolytic properties similar to diazepam. After long period of exposure to stressors, including restrained stress, depressive-like behavior can be produced. BEO has been suggested to reduce depression. However, there is no scientific evidence supporting this property. To investigate the effect of BEO in chronic stressed rats on: 1) behavior related depressive disorder, 2) hypothalamic pituitary adrenal (HPA) axis response, and iii) brain-derived neurotrophic factor (BDNF) protein levels in hippocampus. Male Wistar rats, weighing 200 to 250 g, were induced chronic restrained stress 15 minutes dailyfor two weeks. For the next two weeks, these rats were divided intofour groups, control-i.p., fluoxetine-i.p., control-inhale, and BEO-inhale. Fluoxetine (10 mg/kg i.p.) or saline was intraperitoneally administered daily while 2.5% BEO or saline was inhaled daily. At the end of the treatment, rats were assessed for depressive-like behavior using the forced swimming test (FST). After the behavioral test, the animals were immediately decapitated and trunk blood samples were collected for the measurement ofcorticosterone and adrenocorticotropic hormone (ACTH) levels and hippocampus was dissected and stored in afreezer at -80 °C until assay for BDNF protein. BEO andfluoxetine significantly decreased the immobility time in the FST (p BDNF protein determination, neither BEO norfluoxetine had any effect on BDNF protein levels in hippocampus compared to their controls. The inhalation ofBEO decrease behavior related depressive disorder similar tofluoxetine but has no effect on HPA axis response and BDNF protein levels in chronic restrained stress.

  19. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

    Science.gov (United States)

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

  20. [Open-field behavioral study in rat hyperlipidemia combined with chronic unpredictable mild stress model].

    Science.gov (United States)

    Hu, Hua; Zhang, Yingchun; Xu, Yeqing; Liu, Chunfeng; Wang, Liwei

    2015-06-16

    To investigate behavioral changes in a rat hyperlipidemia model induced by high lipid feed combined with depression by Chronic Unpredictable Mild Stress (CUMS). A total of 40 rats were randomly divided into control (CON), control feed for 9 weeks followed by CUMS for 4 weeks (CON + CUMS), high fat diet (HFD) and high lipid feed for 9 weeks followed by CUMS for 4 weeks (HFD + CUMS) (n = 10 each). Open-field test was individually measured at baseline, week 9 and week 13. (1) Serum lipids: total cholesterol [(2.67 ± 0.04) mmol/L, (2.68 ± 0.02) mmol/L] and low density lipoprotein [(1.08 ± 0.03) mmol/L, (1.06 ± 0.01) mmol/L] of HFD and HFD + CUMS were both significantly higher than those of CON and CON + CUMS [(1.78 ± 0.12) mmol/L, (0.79 ± 0.04) mmol/L; (1.76 ± 0.09) mmol/L, (0.76 ± 0.06) mmol/L, all P Open-field test: at week 13, compared to CON rats, CON + CUMS rats exhibited enhanced locomotor activity during the first minute, reduced activity in the center squares and rearing, and increased the number of grooming and defecation (all P < 0.05). In comparison to the CON rats, a decrease in total squares in 5 min, central squares and peripheral squares was observed in HFD rats at week 13 (all P < 0.05). However, compared with HFD, CON, CON + CUMS rats, when high lipid feed for 9 weeks combined with depression, significant decrease activities in total squares in 5 min, central squares and peripheral squares were observed in HFD + CUMS rats at week 13. Besides these, the number of rearing was reduced, however, locomotor activity during the first minute and the number of grooming and defecation was significantly increased (all P < 0.001). Under uncontrolled hyperlipidemia, severe depressive symptoms will present more early once exposure to a series of chronic stressors followed by significant autonomic nervous dysfunctional symptoms.

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

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    Jennifer L. Cornish

    2012-09-01

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

  2. Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

    Science.gov (United States)

    Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

    2013-05-01

    The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

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

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    Kenichi Nakahara

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

  4. Reproductive effects of the psychoactive beverage ayahuasca in male Wistar rats after chronic exposure

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    Alana de Fátima Andrade Santos

    Full Text Available Abstract Ayahuasca is a psychoactive beverage used ancestrally by indigenous Amazonian tribes and, more recently, by Christian religions in Brazil and other countries. This study aimed to investigate the reproductive effects of this beverage in male Wistar rats after chronic exposure. The rats were treated by gavage every other day for 70 days at 0 (control, 1×, 2×, 4× and 8× the dose used in a religious ritual (12 animals per group, and animals euthanized on the 71st day. Compared to controls, there was a significant decrease in food consumption and body weight gain in rats from the 4× and 8× groups, and a significant increase in the brain and stomach relative weight at the 8× group. There was a significant increase in total serum testosterone, and a decrease in spermatic transit time and spermatic reserves in the epididymis caudae in the 4× group, but not in the highest dose group. No significant changes were found in the other reproductive endpoints (spermatozoid motility and morphology, total spermatozoid count and daily sperm production, and histology of testis and epididymis. This study identified a no-observed-adverse-effect-level for chronic and reproductive effects of ayahuasca in male Wistar rats at 2× the ritualistic dose, which corresponds in this study to 0.62 mg/kg bw N, N-dimethyltryptamine, 6.6 mg/kg bw harmine and 0.52 mg/kg bw harmaline. A potential toxic effect of ayahuasca in male rats was observed at the 4× dose, with a non-monotonic dose–response. Studies investigating the role of ayahuasca components in regulating testosterone levels are needed to better understand this action.

  5. [A comparative study on behaviors of two depression models in rats induced by chronic forced swimming stress].

    Science.gov (United States)

    Han, Ming-Fei; Gao, Dong; Sun, Xue-Li

    2010-01-01

    To compare the behaviors of rats with depressions induced by chronic forced swimming stress under two different conditions. Eighteen male rats were randomly divided into 3 groups, with 6 rats in each group. The rats in the control group (C group) were not forced into swimming, while the rats in the stress groups (S1 and S2) were forced to swim for 14 consecutive days. The rats in S1 group and S2 group swam for five minutes every morning, in water with (23 +/- 1) degree C, and (10 +/- 0.5) degree C in temperature, respectively. The weight gain, food intake, open-field test and saccharin solution test were observed on the seventh day and fourteenth day. On the seventh day following chronic swim stress, the rats in the S2 group had significant lower ratio in weight gain and food intake than the controls (P forced swimming. On the fourteenth day, the rats in the S1 group still had lower ratio in weight gain, but had higher ratio in food intake and preference for saccharin solution, and greater number of crossing than the controls. Chronic forced swimming at a lower temperature could induce depression better than at a higher temperature.

  6. Chronic ethanol tolerance as a result of free-choice drinking in alcohol-preferring rats of the WHP line.

    Science.gov (United States)

    Dyr, Wanda; Taracha, Ewa

    2012-01-01

    The development of tolerance to alcohol with chronic consumption is an important criterion for an animal model of alcoholism and may be an important component of the genetic predisposition to alcoholism. The aim of this study was to determine whether the selectively bred Warsaw High Preferring (WHP) line of alcohol-preferring rats would develop behavioral and metabolic tolerance during the free-choice drinking of ethanol. Chronic tolerance to ethanol-induced sedation was tested. The loss of righting reflex (LRR) paradigm was used to record sleep duration in WHP rats. Ethanol (EtOH)-naive WHP rats received a single intraperitoneal (i.p.) injection of 5.0 g ethanol/kg body weight (b.w.), and sleep duration was measured. Subsequently, rats had access to a 10% ethanol solution under a free-choice condition with water and food for 12 weeks. After 12 weeks of the free-choice intake of ethanol, the rats received another single i.p. injection of 5.0 g ethanol/kg b.w., and sleep duration was reassessed. The blood alcohol content (BAC) for each rat was determined after an i.p. injection of 5 g/kg of ethanol in naive rats and again after chronic alcohol drinking at the time of recovery of the righting reflex (RR). The results showed that the mean ethanol intake was 9.14 g/kg/24 h, and both sleep duration and BAC were decreased after chronic ethanol intake. In conclusion, WHP rats exposed to alcohol by free-choice drinking across 12 weeks exhibited increased alcohol elimination rates. Studies have demonstrated that WHP rats after chronic free-choice drinking (12 weeks) of alcohol develop metabolic tolerance. Behavioral tolerance to ethanol was demonstrated by reduced sleep duration, but this decrease in sleep duration was not significant.

  7. Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

    Science.gov (United States)

    Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

    2018-02-01

    Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain. Copyright © 2017 by the Research Society on Alcoholism.

  8. Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure

    International Nuclear Information System (INIS)

    Bensoussan, Helene; Grancolas, Line; Dhieux-Lestaevel, Bernadette; Delissen, Olivia; Vacher, Claire-Marie; Dublineau, Isabelle; Voisin, Philippe; Gourmelon, Patrick; Taouis, Mohammed; Lestaevel, Philippe

    2009-01-01

    Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor β2 sub-unit (nAChRβ2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.

  9. Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) induced by immunization with a novel peptide T2.

    Science.gov (United States)

    Ihsan, Awais Ullah; Khan, Farhan Ullah; Nawaz, Waqas; Khan, Muhammad Zahid; Yang, Mengqi; Zhou, Xiaohui

    2017-07-01

    The exact etiological mechanism of Chronic Prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be beneficial in elucidating mechanisms involved in the pathogenesis of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). 40 male Sprague-Dawley rats with an average weight of 180-220g were equally distributed into five groups. The normal control group was injected with normal saline (.9% NACL), the CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA. Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin staining and Immunohistochemistry were used to investigate inflammatory cell infiltration and IL-1β in the prostate tissue respectively. ELISA technique was used to measure the serum level of CRP and TNF-α. T-test was used to analyze the results. Maximum infiltration of inflammatory cells and the highest level of IL-1β in the prostate tissue was observed in T2+AL(OH)3+CFA group as revealed by histopathology and Immunohistochemistry, respectively. Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-α and CRP as determined by ELISA technique. Our results demonstrated that T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We believe that our present model will be highly beneficial for investigation of the pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-04-01

    Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

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    Yanxia Lu

    Full Text Available This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9, CMS+fluoxetine (n = 9 and the control (n = 6 groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05. There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

  12. Insulin resistance in uremia: Insulin receptor kinase activity in liver and muscle from chronic uremic rats

    International Nuclear Information System (INIS)

    Cecchin, F.; Ittoop, O.; Sinha, M.K.; Caro, J.F.

    1988-01-01

    The authors have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. 125 I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the β-subunit and insulin receptor kinase activity using Glu 80 , Tyr 20 as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristics of the receptors, as determined by electrophoretic mobilities of affinity labeled α-subunit and the phosphorylated β-subunit, were normal in uremia. 125 I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus the data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase

  13. Changes in proinflammatory cytokines and white matter in chronically stressed rats

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    Yang P

    2015-03-01

    Full Text Available Ping Yang,1 Zhenyong Gao,1 Handi Zhang,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Qing-Jun Huang1 1Mental Health Center, 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies. Keywords: cytokines, depression, myelination, oligodendrocytes, stress 

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

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    Éder Ricardo Biasoli

    2009-01-01

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

  15. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

    Science.gov (United States)

    Lu, Yanxia; Ho, Cyrus S; Liu, Xin; Chua, Anna N; Wang, Wei; McIntyre, Roger S; Ho, Roger C

    2017-01-01

    This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (pfluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

  16. Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

    Science.gov (United States)

    Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

    2010-12-17

    Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Resveratrol Improves Cell Cycle Arrest in Chronic Prostatitis Rats, by C-kit/SCF Suppression.

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    He, Yi; Zeng, Huizhi; Yu, Yang; Zhang, Jiashu; Zeng, Xiaona; Gong, Fengtao; Liu, Qi; Yang, Bo

    2017-08-01

    Chronic prostatitis (CP) with complex pathogenesis is difficult for treatment. c-kit has been associated with the control of cell proliferation of prostate cells. This study aims to evaluate the role of resveratrol, an activator of Sirt1, in regulating the expression of c-kit in CP and investigate the consequent effects on cell cycle. Rat model of CP was established through subcutaneous injections of diphtheria-pertussis-tetanus vaccine and subsequently treated with resveratrol. Hematoxylin and eosin staining was performed to identify the histopathological changes in prostates. Western blotting and immunohistochemical staining examined the expression level of c-kit, stem cell factor (SCF), Sirt1, and cell cycle-associated proteins. The model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Gland lumen diameter was also significantly smaller; the activity of c-kit/SCF in the CP rats was increased significantly compared to the control group. Meanwhile, the cell cycle proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. Dysregulation of cell cycle was involved in the pathological processes of CP, which was improved after resveratrol treatment by the downregulation of c-kit/SCF by activating Sirt1.

  18. The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

    Science.gov (United States)

    Yang, Yang; He, Qin; Wang, Hong; Hu, Xinyue; Luo, Ying; Liang, Guojuan; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Tian, Xiaoyan; Chen, Qi; Yang, Junqing

    2017-04-04

    The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

  19. Testicular immunohistochemical and Ultrastructural changes associated with chronic cholestasis in rats: Effect of ursodeoxycholic acid.

    Science.gov (United States)

    Mahmoud, Yomna I

    2015-09-01

    Testicular atrophy has been commonly reported in patients with chronic liver diseases. Ursodeoxycholic acid is the most widely used drug for the treatment of many liver diseases. However, its effect on testicular ultrastructure associated with chronic cholestasis has never been studied. Thus, this study aimed to assess how chronic obstructive jaundice affects the testicular ultrastructure and whether it affects the androgen receptor or the proliferating cell nuclear antigen. The role of ursodeoxycholic acid was also investigated. Cholestasis was induced by bile duct ligation. Samples were collected 4weeks postoperative. Testicular changes were assessed using immunohistochemistry and transmission electron microscopy. Chronic cholestasis resulted in testicular atrophy evidenced by shrinkage and deformation of seminiferous tubules, thickening of peritubular boundaries, vacuolation, disorganization of germ cells, and maturation arrest. This was accompanied by decreased immunoreactivity of androgen receptors and proliferating cell nuclear antigen. Administration of ursodeoxycholic acid improved the testicular morphology and reversed cholestasis-induced immunohistochemical and ultrastructural changes. Ursodeoxycholic acid can improve the testicular ultrastructure and restore the spermatogenic process in rats with chronic cholestasis. These findings support the clinical application of ursodeoxycholic acid in cholestatic patients especially those with hypogonadism. Copyright © 2015. Published by Elsevier Inc.

  20. Subacute stress and chronic stress interact to decrease intestinal barrier function in rats.

    Science.gov (United States)

    Lauffer, Adriana; Vanuytsel, Tim; Vanormelingen, Christophe; Vanheel, Hanne; Salim Rasoel, Shadea; Tóth, Joran; Tack, Jan; Fornari, Fernando; Farré, Ricard

    2016-01-01

    Psychological stress increases intestinal permeability, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders. We assessed the effect of subacute, chronic and combined stress on intestinal barrier function and mast cell density. Male Wistar rats were allocated to four experimental groups (n = 8/group): 1/sham; 2/subacute stress (isolation and limited movement for 24 h); 3/chronic crowding stress for 14 days and 4/combined subacute and chronic stress. Jejunum and colon were collected to measure: transepithelial electrical resistance (TEER; a measure of epithelial barrier function); gene expression of tight junction molecules; mast cell density. Plasma corticosterone concentration was increased in all three stress conditions versus sham, with highest concentrations in the combined stress condition. TEER in the jejunum was decreased in all stress conditions, but was significantly lower in the combined stress condition than in the other groups. TEER in the jejunum correlated negatively with corticosterone concentration. Increased expression of claudin 1, 5 and 8, occludin and zonula occludens 1 mRNAs was detected after subacute stress in the jejunum. In contrast, colonic TEER was decreased only after combined stress, and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the chronic and combined stress condition in the colon only. In conclusion, our data show that chronic stress sensitizes the gastrointestinal tract to the effects of subacute stress on intestinal barrier function; different underlying cellular and molecular alterations are indicated in the small intestine versus the colon.

  1. 5-lipoxygenase activation is involved in the mechanisms of chronic hepatic injury in a rat model of chronic aluminum overload exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Shaoshan [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China); He, Qin [Department of Heptobiliary Surgery, 1st Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China); Wang, Hong; Hu, Xinyue; Luo, Ying; Yang, Yang; Kuang, Shengnan; Tian, Xiaoyan; Ma, Jie [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China); Yang, Junqing, E-mail: 1139627371@qq.com [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China)

    2016-08-15

    We previously confirmed that rats overloaded with aluminum exhibited hepatic function damage and increased susceptibility to hepatic inflammation. However, the mechanism of liver toxicity by chronic aluminum overload is poorly understood. In this study, we investigated changes in the 5-lipoxygenase (5-LO) signaling pathway and its effect on liver injury in aluminum-overloaded rats. A rat hepatic injury model of chronic aluminum injury was established via the intragastric administration of aluminum gluconate (Al{sup 3+} 200 mg/kg per day, 5 days a week for 20 weeks). The 5-LO inhibitor, caffeic acid (10 and 30 mg/kg), was intragastrically administered 1 h after aluminum administration. Hematoxylin and eosin staining was used to visualize pathological changes in rat liver tissue. A series of biochemical indicators were measured with biochemistry assay or ELISAs. Immunochemistry and RT-PCR methods were used to detect 5-LO protein and mRNA expression in the liver, respectively. Caffeic acid administration protected livers against histopathological injury, decreased plasma ALT, AST, and ALP levels, decreased TNF-α, IL-6, IL-1β and LTs levels, increased the reactive oxygen species content, and down-regulated the mRNA and protein expressions of 5-LO in aluminum overloaded rats. Our results indicate that 5-lipoxygenase activation is mechanistically involved in chronic hepatic injury in a rat model of chronic aluminum overload exposure and that the 5-LO signaling pathway, which associated with inflammation and oxidative stress, is a potential therapeutic target for chronic non-infection liver diseases. - Highlights: • 5-LO signaling contributes to mechanisms of hepatotoxicity of aluminum overload. • Oxidative and inflammatory reaction involve in chonic aluminum hepatotoxicity. • 5-LO inhibitor has a protective effect on aluminum-overload liver injury. • 5-LO signaling is a potential therapeutic target for non-infection liver diseases.

  2. Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats

    Directory of Open Access Journals (Sweden)

    Anil Kumar Saxena

    2015-06-01

    Full Text Available Aging related reduction in cerebral blood flow (CBF has been linked with neurodegenerative disorders including Alzheimer's disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO in rats. Since oxidative stress, leading to neuronal apoptosis and death, is one of the mechanisms, which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the ROS status by measuring the levels of anti-oxidant enzymes that might occur during chronic cerebral hypoperfusion. Antioxidant enzymes namely glutathione peroxidase (GPx, superoxide dismutase (SOD, and catalase were measured in the brain tissue at eight weeks of 2VO induction in rats. Results show significantly elevated levels of GPx, SOD, and catalase enzymes as compared with the control group. It is possible that compensatory rise in antioxidant enzymes occurs in response to increased oxidative stress following ischemic insult.

  3. Acute and chronic dosing of Lepidium meyenii (Maca) on male rat sexual behavior.

    Science.gov (United States)

    Lentz, Aaron; Gravitt, Karla; Carson, Culley C; Marson, Lesley

    2007-03-01

    The use of natural remedies for the treatment of sexual disorders is under current investigation. For generations people of the rural community in Peru have used Lepidium meyenii Walpers (Maca), because of their belief that it improves fertility and sexual desire. To determine the acute and chronic effects of Maca on male sexual behavior and to examine chronic administration of Maca on anxiety. Ejaculatory and mounting behavior and postejaculatory interval. Anxiety tests using an elevated plus maze, locomotion, and social interaction with another male. Maca (25 and 100 mg/kg) was orally administered to male rats for 30 days. Male sexual behavior was monitored after acute, 7 and 21 days of treatment. Anxiety behavior and locomotion were measured at 28-29 days using the elevated plus maze and social interaction tests. Maca treatment did not produce large changes in male sexual behavior. However, an increase in ejaculation latency and postejaculatory interval was observed after both acute and 7 days of treatment. After 21 days of treatment Maca had no effect on sexual behavior. Chronic administration of Maca did not increase locomotion or anxiety. Acute and short-term administration of Maca produced a small effect of rat male sexual behavior and long-term administration did not increase anxiety.

  4. Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection.

    Science.gov (United States)

    Song, Z; Johansen, H K; Moser, C; Høiby, N

    1996-05-01

    The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable.

  5. Chronic stress associated with hypercaloric diet changes the hippocampal BDNF levels in male Wistar rats.

    Science.gov (United States)

    Macedo, I C; Rozisky, J R; Oliveira, C; Oliveira, C M; Laste, G; Nonose, Y; Santos, V S; Marques, P R; Ribeiro, M F M; Caumo, W; Torres, I L S

    2015-06-01

    Chronic stress, whether associated with obesity or not, leads to different neuroendocrine and psychological changes. Obesity or being overweight has become one of the most serious worldwide public health problems. Additionally, it is related to a substantial increase in daily energy intake, which results in substituting nutritionally adequate meals for snacks. This metabolic disorder can lead to morbidity, mortality, and reduced quality of life. On the other hand, brain-derived neurotrophic factor (BDNF) is widely expressed in all brain regions, particularly in the hypothalamus, where it has important effects on neuroprotection, synaptic plasticity, mammalian food intake-behavior, and energy metabolism. BDNF is involved in many activities modulated by the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, this study aims to evaluate the effect of obesity associated with chronic stress on the BDNF central levels of rats. Obesity was controlled by analyzing the animals' caloric intake and changes in body weight. As a stress parameter, we analyzed the relative adrenal gland weight. We found that exposure to chronic restraint stress during 12 weeks increases the adrenal gland weight, decreases the BDNF levels in the hippocampus and is associated with a decrease in the calorie and sucrose intake, characterizing anhedonia. These effects can be related stress, a phenomenon that induces depression-like behavior. On the other hand, the rats that received the hypercaloric diet had an increase in calorie intake and became obese, which was associated with a decrease in hypothalamus BDNF levels. Copyright © 2015. Published by Elsevier Ltd.

  6. Chinese herbal medicine Shenqi Detoxification Granule inhibits fibrosis in adenine induced chronic renal failure rats.

    Science.gov (United States)

    Peng, Min; Cai, Pingping; Ma, Hongbo; Meng, Hongyan; Xu, Yuan; Zhang, Xiaoyi; Si, Guomin

    2014-01-01

    Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.

  7. Effects of Chronic and Acute Zinc Supplementation on Myocardial Ischemia-Reperfusion Injury in Rats.

    Science.gov (United States)

    Ozyıldırım, Serhan; Baltaci, Abdulkerim Kasim; Sahna, Engin; Mogulkoc, Rasim

    2017-07-01

    The present study aims to explore the effects of chronic and acute zinc sulfate supplementation on myocardial ischemia-reperfusion injury in rats. The study registered 50 adult male rats which were divided into five groups in equal numbers as follows: group 1, normal control; group 2, sham; group 3, myocardial ischemia reperfusion (My/IR): the group which was fed on a normal diet and in which myocardial I/R was induced; group 4, myocardial ischemia reperfusion + chronic zinc: (5 mg/kg i.p. zinc sulfate for 15 days); and group 5, myocardial ischemia reperfusion + acute zinc: the group which was administered 15 mg/kg i.p. zinc sulfate an hour before the operation and in which myocardial I/R was induced. The collected blood and cardiac tissue samples were analyzed using spectrophotometric method to determine levels of MDA, as an indicator of tissue injury, and GSH, as an indicator of antioxidant activity. The highest plasma and heart tissue MDA levels were measured in group 3 (p zinc administration and markedly by chronic zinc supplementation.

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

    Science.gov (United States)

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

    2015-10-01

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

  9. Chronic intermittent hypoxia promotes expression of 3-mercaptopyruvate sulfurtransferase in adult rat medulla oblongata.

    Science.gov (United States)

    Li, Mingqiang; Nie, Lihong; Hu, Yajie; Yan, Xiang; Xue, Lian; Chen, Li; Zhou, Hua; Zheng, Yu

    2013-12-01

    The present experiments were carried out to investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of rats and effects of chronic intermittent hypoxia (CIH) on its expression. Sprague Dawley adult rats were randomly divided into two groups, including control (Con) group and CIH group. The endogenous production of hydrogen sulfide (H2S) in medulla oblongata tissue homogenates was measured using the methylene blue assay method, 3MST mRNA and protein expression were analyzed by RT-PCR and Western blotting, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of rats was investigated with immunohistochemical technique. CIH elevated the endogenous H2S production in rat medulla oblongata (Pmedulla oblongata of rats and CIH promoted their expression (P<0.01). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N and Amb, but not in FN and NTS, were significantly increased in CIH group (P<0.05). In conclusion, 3MST exists in the neurons of medullary respiratory nuclei and its expression can be up-regulated by CIH in adult rat, suggesting that 3MST-H2S pathway may be involved in regulation of respiration and protection on medullary respiratory centers from injury induced by CIH. © 2013.

  10. Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

    International Nuclear Information System (INIS)

    Minor, Robin K.; Smith, Daniel L.; Sossong, Alex M.; Kaushik, Susmita; Poosala, Suresh; Spangler, Edward L.; Roth, George S.; Lane, Mark; Allison, David B.; Cabo, Rafael de; Ingram, Donald K.; Mattison, Julie A.

    2010-01-01

    Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

  11. Effects of chronic mild stress on parameters of bone assessment in adult male and female rats

    Directory of Open Access Journals (Sweden)

    Fabrício L. Valente

    Full Text Available Abstract: Osteoporosis is a multifactorial disease of high prevalence and has great impact on quality of life, because the effects on bone structure increase the risk of fractures, what may be very debilitating. Based on the observation that patients with depression have lower bone mineral density than healthy individuals, many studies have indicated that stress could be an aggravating factor for bone loss. This study evaluates the effect of a protocol of chronic mild stress (CMS on parameters of bone assessment in male and female rats. Five 5-monh-old rats of each sex underwent a schedule of stressor application for 28 days. Stressors included cold, heat, restraint, cage tilt, isolation, overnight illumination, and water and food deprivation. Five rats of each sex were kept under minimum intervention as control group. The animals were weighed at beginning and end of the period, and after euthanasia had their bones harvested. Femur, tibia and lumbar vertebrae were analyzed by bone densitometry. Biomechanical tests were performed in femoral head and diaphysis. Trabecular bone volume was obtained from histomorphometric analysis of femoral head and vertebral body, as well as of femoral midshaft cross-sectional measures. Not all parameters analyzed showed effect of CMS. However, tibial and L4 vertebral bone mineral density and cross-sectional cortical/medullar ratio of femoral shaft were lower in female rats submitted to the CMS protocol. Among male rats, the differences were significant for femoral trabecular bone volume and maximum load obtained by biomechanical test. Thus, it could be confirmed that CMS can affect the balance of bone homeostasis in rats, what may contribute to the establishment of osteopenia or osteoporosis.

  12. Ventilatory drive is enhanced in male and female rats following chronic intermittent hypoxia.

    Science.gov (United States)

    Edge, D; Skelly, J R; Bradford, A; O'Halloran, K D

    2009-01-01

    Obstructive sleep apnoea is characterized by chronic intermittent hypoxia (CIH) due to recurrent apnoea. We have developed a rat model of CIH, which shows evidence of impaired respiratory muscle function. In this study, we wished to characterize the ventilatory effects of CIH in conscious male and female animals. Adult male (n=14) and female (n=8) Wistar rats were used. Animals were placed in chambers daily for 8 h with free access to food and water. The gas supply to one half of the chambers alternated between air and nitrogen every 90 s, for 8 h per day, reducing ambient oxygen concentration in the chambers to 5% at the nadir (intermittent hypoxia; n=7 male, n=4 female). Air supplying the other chambers was switched every 90 s to air from a separate source, at the same flow rates, and animals in these chambers served as controls (n=7 male, n=4 female). Ventilatory measurements were made in conscious animals (typically sleeping) after 10 days using whole-body plethysmography. Normoxic ventilation was increased in both male and female CIH-treated rats compared to controls but this did not achieve statistical significance. However, ventilatory drive was increased in CIH-treated rats of both sexes as evidenced by significant increases in mean and peak inspiratory flow. Ventilatory responses to acute hypoxia (F(I)O(2) = 0.10; 6 min) and hyperoxic hypercapnia (F(I)CO(2) = 0.05; 6 min) were unaffected by CIH treatment in male and female rats (P>0.05, ANOVA). We conclude that CIH increases respiratory drive in adult rats. We speculate that this represents a form of neural plasticity that may compensate for respiratory muscle impairment that occurs in this animal model.

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

    Directory of Open Access Journals (Sweden)

    Botezelli Jose D

    2010-06-01

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

  14. Changes of plasma angiogenic factors during chronic resistance exercise in type 1 diabetic rats

    International Nuclear Information System (INIS)

    Esfahani, S.P.; Gharakhanlou, R.

    2012-01-01

    Objective: Exercise has several beneficial effects on cardiovascular system. However, the exact mechanism is unclear. The purpose of this study was to evaluate the effects of chronic resistance exercise on some plasma angiogenic factors in type 1 diabetic rats. Methodology: Thirty male Wistar rats were divided into three groups of control, diabetic and diabetic trained (n = 10 each). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). The rats in the trained group undertook one training session per day, 3 days/week, for 4 weeks. Blood samples were taken and the concentrations of plasma glucose, lipid profile, nitric oxide (NO), vascular endothelial growth factor (VEGF) and soluble form of VEGF receptor-1 (sFlt-1) were determined. Results: We found a significant reduction in plasma NO concentrations in diabetic rats compared to the controls (p 0.05). There were no significant differences in plasma VEGF and sFlt-1 concentrations between diabetic sedentary and trained groups (p > 0.05). Moreover, VEGF/sFlt-1 ratios in diabetic animals were lower than the control group and resistance exercise could not increase this ratio in diabetic animals (p > 0.05) Conclusion: Resistance exercise could not change plasma VEGF, sFlt-1 and VEGF/sFlt-1 ratio. However, it increased plasma NO concentrations in diabetic animals. More studies are needed to determine the effects of this type of exercise on the angiogenesis process. (author)

  15. Protective effects of chronic mild stress during adolescence in the low-novelty responder rat.

    Science.gov (United States)

    Rana, Samir; Nam, Hyungwoo; Glover, Matthew E; Akil, Huda; Watson, Stanley J; Clinton, Sarah M; Kerman, Ilan A

    2016-01-01

    Stress-elicited behavioral and physiologic responses vary widely across individuals and depend on a combination of environmental and genetic factors. Adolescence is an important developmental period when neural circuits that guide emotional behavior and stress reactivity are still maturing. A critical question is whether stress exposure elicits contrasting effects when it occurs during adolescence versus adulthood. We previously found that Sprague-Dawley rats selectively bred for low-behavioral response to novelty (bred Low Responders; bLRs) are particularly sensitive to chronic unpredictable mild stress (CMS) exposure in adulthood, which exacerbates their typically high levels of spontaneous depressive- and anxiety-like behavior. Given developmental processes known to occur during adolescence, we sought to determine whether the impact of CMS on bLR rats is equivalent when they are exposed to it during adolescence as compared with adulthood. Young bLR rats were either exposed to CMS or control condition from postnatal days 35-60. As adults, we found that CMS-exposed bLRs maintained high levels of sucrose preference and exhibited increased social exploration along with decreased immobility on the forced swim test compared with bLR controls. These data indicate a protective effect of CMS exposure during adolescence in bLR rats.

  16. Hepatic cholesterol metabolism following a chronic ingestion of cesium-137 starting at fetal stage in rats

    International Nuclear Information System (INIS)

    Racine, R.; Grandcolas, L.; Blanchardon, E.; Gourmelon, P.; Souidi, M.; Veyssiere, G.

    2010-01-01

    The Chernobyl accident released many radionuclides in the environment. Some are still contaminating the ground and thus the people through dietary intake. The long-term sanitary consequences of this disaster are still unclear and several biological systems remain to be investigated. Cholesterol metabolism is of particular interest, with regard to the link established between atherosclerosis and exposure to high-dose ionizing radiations. This study assesses the effect of cesium-137 on cholesterol metabolism in rats, after a chronic exposure since fetal life. To achieve this, rat dams were contaminated with cesium-137-supplemented water from two weeks before mating until the weaning of the pups. Thereafter, the weaned rats were given direct access to the contaminated drinking water until the age of 9 months. After the sacrifice, cholesterol metabolism was investigated in the liver at gene expression and protein level. The cholesterolemia was preserved, as well as the cholesterol concentration in the liver. At molecular level, the gene expressions of ACAT 2 (a cholesterol storage enzyme), of Apolipoprotein A-I and of RXR (a nuclear receptor involved in cholesterol metabolism) were significantly decreased. In addition, the enzymatic activity of CYP27A1, which catabolizes cholesterol, was increased. The results indicate that the rats seem to adapt to the cesium-137 contamination and display modifications of hepatic cholesterol metabolism only at molecular level and within physiological range. (author)

  17. Behavioural effects of chronic manipulations of dietary choline in senescent rats.

    Science.gov (United States)

    Fundaro, A; Paschero, A

    1990-01-01

    1. Senescent rats were maintained on choline-deficient and choline-enriched diets. The modifications in rat behaviour caused by the chronic manipulations of dietary choline were studied in two schedules of operant conditioning. 2. In the "periodic conditioning" test, the schedule of reinforcement, in a 100 min trial, was changed from a fixed ratio to a fixed interval schedule. In the "reversal" test the contingency for food delivery was switched four times from one lever to the other in a two lever Skinner box. 3. In the "periodic conditioning" test, the choline enriched group (430 mg/Kg/day) showed the same reduction of responses/reinforcement as controls, from the beginning to the end of trial; in the same group the time course reduction of responses/reinforcement became significant earlier than in the control group. The deficient-choline group in the last 40 min of "periodic conditioning" trial gave a reduction of responses/reinforcement greater than controls and one rat in the group did not learn the change of experimental schedule and extinguished its operant behaviour. 4. In the "reversal" test, the choline-enriched diet (320 mg/Kg/day) improved the reinforced responses in the IV reversal; one rat of the deficient-choline group could not learn the new operant schedule since the first reversal and continued to respond on the same lever during the whole of the test.

  18. Chronic fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin.

    Science.gov (United States)

    Cantor, J M; Binik, Y M; Pfaus, J G

    1999-06-01

    Selective serotonin reuptake inhibitors, used widely in the treatment of depression, progressively inhibit sexual orgasm in many patients and induce a transient inhibition of sexual desire. We attempted to model the effects of these drugs in sexually experienced male rats during tests of copulation in bilevel chambers. These chambers allow the study of both appetitive and consummatory sexual responses of male rats. Males were treated daily with fluoxetine hydrochloride (0, 1, 5, or 10 mg/kg) and tested for sexual behavior with receptive females at 4-day intervals. Rats were treated with oxytocin (200 ng/kg) or saline after ejaculations had decreased. Fluoxetine decreased ejaculatory responses of male rats in a dose- and time-dependent fashion, but left the copulatory efficiency of the males intact. In contrast, conditioned level changing, a measure of appetitive sexual excitement, was inhibited following acute and chronic treatment with 10 mg/kg, although tolerance may have developed to the effect of 5 mg/kg. Subsequent administration of oxytocin restored the ejaculatory response but not the measure of sexual excitement to baseline levels. The reversal by oxytocin of the fluoxetine-induced deficit in ejaculations is consistent with the hypothesis that serotonin suppresses ejaculatory mechanisms by interrupting the action of oxytocin, which normally accompanies sexual behavior. Co-administration of oxytocin may help to alleviate the predominant sexual side effect of serotonin reuptake blockers.

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

    Science.gov (United States)

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

    2014-10-01

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

  20. Impaired hypoxic ventilatory response following neonatal sustained and subsequent chronic intermittent hypoxia in rats.

    Science.gov (United States)

    Mayer, C A; Ao, J; Di Fiore, J M; Martin, R J; MacFarlane, P M

    2013-06-15

    Neonatal chronic intermittent hypoxia (CIH) enhances the ventilatory sensitivity to acute hypoxia (acute hypoxic ventilatory response, HVR), whereas sustained hypoxia (SH) can have the opposite effect. Therefore, we investigated whether neonatal rats pre-treated with SH prior to CIH exhibit a modified HVR. Rat pups were exposed to CIH (5% O2/5min, 8h/day) between 6 and 15 days of postnatal age (P6-15) after pre-treatment with either normoxia or SH (11% O2; P1-5). Using whole-body plethysmography, the acute (5min, 10% O2) HVR at P16 (1 day post-CIH) was unchanged following CIH (67.9±6.7% above baseline) and also SH (58.8±10.5%) compared to age-matched normoxic rats (54.7±6.3%). In contrast, the HVR was attenuated (16.5±6.0%) in CIH exposed rats pre-treated with SH. These data suggest that while neonatal SH and CIH alone have little effect on the magnitude of the acute HVR, their combined effects impose a synergistic disturbance to postnatal development of the HVR. These data could provide important insight into the consequences of not maintaining adequate levels of oxygen saturation during the early neonatal period, especially in vulnerable preterm infants susceptible to frequent bouts of hypoxemic events (CIH) that are commonly associated with apnea of prematurity. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Effects of an Astragalus Polysaccharide and Rhein Combination on Apoptosis in Rats with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Yonghong Lian

    2014-01-01

    Full Text Available Objective. To investigate the effects and to analyze the mechanism of the combination of Astragalus polysaccharide (APS and Rhein on apoptosis in rats with chronic renal failure (CRF. Methods. Thirty-seven male Wistar rats were randomly divided into a control group, a model group, a low-dose APS and Rhein combination group, and a high-dose APS and Rhein combination group. CRF was induced by orogastric gavage with adenine. Rats were observed for renal function, electrolyte, and pathological changes for 7 weeks after administration. Renal tubular cell apoptosis was assessed by TUNEL and protein expressions of IRE1 and CHOP were detected by Western-blotting. Results. The combination of APS and Rhein decreased the kidney weight and index, improved renal pathological injury, maintained the stability of serum electrolytes, and reduced SCr and BUN levels in rat models. Moreover, APS and Rhein combination could effectively inhibit the apoptosis and reduce the protein expressions of IRE1and CHOP of renal tubular cells. Conclusions. The combination of APS and Rhein could improve renal function and reduce renal cell apoptosis to protect against further progression of CRF, whose mechanism may be related to alleviate endoplasmic reticulum stress (ERS in the renal cells.

  2. Chronic hypoxia suppresses the CO2 response of solitary complex (SC) neurons from rats.

    Science.gov (United States)

    Nichols, Nicole L; Wilkinson, Katherine A; Powell, Frank L; Dean, Jay B; Putnam, Robert W

    2009-09-30

    We studied the effect of chronic hypobaric hypoxia (CHx; 10-11% O(2)) on the response to hypercapnia (15% CO(2)) of individual solitary complex (SC) neurons from adult rats. We simultaneously measured the intracellular pH and firing rate responses to hypercapnia of SC neurons in superfused medullary slices from control and CHx-adapted adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. We found that CHx caused the percentage of SC neurons inhibited by hypercapnia to significantly increase from about 10% up to about 30%, but did not significantly alter the percentage of SC neurons activated by hypercapnia (50% in control vs. 35% in CHx). Further, the magnitudes of the responses of SC neurons from control rats (chemosensitivity index for activated neurons of 166+/-11% and for inhibited neurons of 45+/-15%) were the same in SC neurons from CHx-adapted rats. This plasticity induced in chemosensitive SC neurons by CHx appears to involve intrinsic changes in neuronal properties since they were the same in synaptic blockade medium.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

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

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  5. Microvascular pressure responses of second-generation rats chronically exposed to 2 g centrifugation

    Science.gov (United States)

    Richardson, D. R.; Knapp, C. F.

    1977-01-01

    Preliminary results are presented for a study aimed at a quantitative comparison of microvascular dynamics in second-generation rats reared in a 2-g force field produced by centrifugation with similar data from animals reared in a centrifuge that produced only a 1-g force. It is shown that the pressure distribution in the mesenteric microvasculature of the second generation of rats reared in a 2-g environment, as well as the animals' blood pressure response to epinephrine, are significantly different compared to their 1-g counterparts. In particular, 1-g and 2-g chronic centrifugation enhances the arterial blood pressure, and the 2-g force field attenuates the pressor effects of norepinephrine.

  6. Chronic toxicologic study of the ethanolic extract of the aerial parts of Jatropha gossypiifolia in rats

    Directory of Open Access Journals (Sweden)

    Saulo R. Mariz

    Full Text Available This work presents the observed changes in Wistar rats under long treatment (thirteen weeks with different oral doses of the ethanolic extract (EE from Jatropha gossypiifolia L., Euphorbiaceae. The most significant toxic signs indicated a reduction of the activity in the central nervous system and digestive disturbances. The histopathological analysis shows hepatotoxity and pulmonary damages. The lethality was 46.6% among males under the higher experimental dose (405 mg/kg and 13.3% both in females under the higher dose and among the animals treated with 135 mg/kg of the product. These data show the significant oral chronic toxicity of EE of J. gossypiifolia in rats.

  7. Antiallodynic Effect of Herbal Medicine Yokukansan on Peripheral Neuropathy in Rats with Chronic Constriction Injury

    Directory of Open Access Journals (Sweden)

    Yasuyuki Suzuki

    2012-01-01

    Full Text Available Yokukansan, one of the traditional Japanese herbal medicines, ameliorated neuropathic pain symptoms in patients. In this study, we investigated the effects of yokukansan on neuropathic pain in chronic constriction injury (CCI model. Oral administration of yokukansan significantly inhibited mechanical and cold allodynia in the von Frey hair or acetone test, respectively. In comparison, amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not significant, antiallodynic effects in the mechanical and cold tests. Yokukansan significantly inhibited the cerebrospinal fluid dialysate level of glutamate that had increased by the stimulation of brush or acetone. Glutamate transporter inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that yokukansan was confirmed to have antiallodynic effects in CCI rats, which are related to a blockade of glutamatergic neurotransmission via activation of glutamate transporters in the spinal cord.

  8. Chronic low-level tritium contamination effects on humoral immune response in rats

    International Nuclear Information System (INIS)

    Petcu, I.; Bejan, A.; Stinga, A.

    1993-01-01

    Using an adaptation of the radioimmunoassay technique, the present study reports on immunochemical parameters of the antibodies synthesized in vivo against bovine serum albumin by rats previously exposed to long-term internal contamination with tritiated water. The corresponding dose range of the irradiation was between 0.6 and 6.2 mGy. A slight increase of a affinity constant of the antibodies produced by the irradiated organisms was found. This experimental fact might sustain the hypothesis of a humoral immune response associated to adaptation increase in cell renewal mechanisms, rather than to selective cell deletion. We also observed a total dissimilarity between the modifications induced by chronic low-dose irradiation and those induced by physiological aging. For old rats the concentration of antibodies is higher by almost an order of magnitude, but they are much less efficient as the decreased value of the affinity constant indicates. (Author)

  9. DISTURBANCES OF BIOLOGICAL RHYTHMS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

    validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted circadian......Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent...

  10. Aliskiren prevents the toxic effects of peritoneal dialysis fluids during chronic dialysis in rats.

    Directory of Open Access Journals (Sweden)

    Juan Pérez-Martínez

    Full Text Available The benefits of long-term peritoneal dialysis (PD in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs.

  11. Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure

    Science.gov (United States)

    Wang, Jiali; Xu, Jiankun; Liu, Waiching; Li, Yangde; Qin, Ling

    2016-05-01

    Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns.

  12. The Effect of Chronic Administration of Buspirone on 6-Hydroxydopamine-Induced Catalepsy in Rats

    Directory of Open Access Journals (Sweden)

    Hamdolah Sharifi

    2012-06-01

    Full Text Available Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-hydroxydopamine (6-OHDA and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p. administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days was assessed in 6-OHDA-lesioned rats. Results: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl- 4-[4-(2-phthalimido butyl]piperazine hydrobromide (NAN-190, 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist. Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD. We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.

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

    International Nuclear Information System (INIS)

    Tissandie, E.; Gueguen, Y.; Lobaccaro, J.M.A.; Aigueperse, J.; Gourmelon, P.; Paquet, F.; Souidi, M.

    2006-01-01

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

  14. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

    Science.gov (United States)

    Desjardins, Stephane; Belkai, Emilie; Crete, Dominique; Cordonnier, Laurie; Scherrmann, Jean-Michel; Noble, Florence; Marie-Claire, Cynthia

    2008-12-01

    Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, the behavioral signs of spontaneous withdrawal were observed and a withdrawal score was determined. This score enabled to select the time points at which the animals displayed the mildest and strongest withdrawal signs (12 h and 36 h after the last injection). Oligonucleotide arrays were used to assess differential gene expression in the PBMCs and quantitative real-time RT-PCR to validate the modulation of several candidate genes 12 h and 36 h after the last injection. Among the 812 differentially expressed candidates, several genes (Adcy5, Htr2a) and pathways (Map kinases, G-proteins, integrins) have already been described as modulated in the brain of morphine-treated rats. Sixteen out of the twenty-four tested candidates were validated at 12 h, some of them showed a sustained modulation at 36 h while for most of them the modulation evolved as the withdrawal score increased. This study suggests similarities between the gene expression profile in PBMCs and brain of morphine-treated rats. Thus, the searching of correlations between the severity of the withdrawal and the PBMCs gene expression pattern by transcriptional analysis of blood cells could be promising for the study of the mechanisms of addiction.

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

    Directory of Open Access Journals (Sweden)

    Jessica Godfrey

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

  16. A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

    Directory of Open Access Journals (Sweden)

    Ellen Neven

    Full Text Available The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF. In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

  17. hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Antti Siltanen

    2011-04-01

    Full Text Available After severe myocardial infarction (MI, heart failure results from ischemia, fibrosis, and remodeling. A promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in MI is myoblast sheet transplantation. We hypothesized that in a rat model of MI-induced chronic heart failure, this therapy could be further improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF in the myoblast sheets. We studied the ability of wild type (L6-WT and human HGF-expressing (L6-HGF L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression profiles by use of microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD ligation and allowed heart failure to develop for 4 weeks. Thereafter, we administered L6-WT (n = 15 or L6-HGF (n = 16 myoblast sheet therapy. Control rats (n = 13 underwent LAD ligation and rethoracotomy without therapy, and five rats underwent a sham operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy, and analyzed cardiac angiogenesis and left ventricular architecture from histological sections at 4 weeks. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further

  18. Influence of omega-3 fatty acid status on the way rats adapt to chronic restraint stress.

    Directory of Open Access Journals (Sweden)

    Marie Hennebelle

    Full Text Available Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF activity, anxiety in the elevated-plus maze (EPM, the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test and entries into the open arms (EPM. Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress.

  19. Effect of chronic psychogenic stress on some behavioral and neurochemical characteristics of rats

    International Nuclear Information System (INIS)

    Danchev, N.D.; Rozhanets, V.V.; Val'dman, A.V.

    1986-01-01

    This paper studies the behavioral, somatic, and certain neurochemical parameters in rats under conditions of unavoidable chronic stress, according to Hecht et al. in a situation of possible avoidance, with the same total number of aversive stimuli. Specific binding of tritium-flunitrazepam and tritium-dihydroalprenolol was studied. The dissociatin constant and the maximal concentration of ligand-receptor complexes were determined in Scatchard plots by means of an HP-33E computer. The protein concentration in the samples was determined by Peterson's method

  20. Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats.

    Science.gov (United States)

    Killian, Megan L; Cavinatto, Leonardo M; Ward, Samuel R; Havlioglu, Necat; Thomopoulos, Stavros; Galatz, Leesa M

    2015-10-01

    Chronic rotator cuff tears present a clinical challenge, often with poor outcomes after surgical repair. Degenerative changes to the muscle, tendon, and bone are thought to hinder healing after surgical repair; additionally, the ability to overcome degenerative changes after surgical repair remains unclear. The purpose of this study was to evaluate healing outcomes of muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff disease and to compare these outcomes to those of acute rotator cuff injuries and repair. The hypothesis was that degenerative rotator cuff changes associated with chronic multitendon tears and muscle unloading would lead to poor structural and mechanical outcomes after repair compared with acute injuries and repair. Controlled laboratory study. Chronic rotator cuff injuries, induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons and injection of botulinum toxin A into the SS and IS muscle bellies, were created in the shoulders of rats. After 8 weeks of injury, tendons were surgically reattached to the humeral head, and an acute, dual-tendon injury and repair was performed on the contralateral side. After 8 weeks of healing, muscles were examined histologically, and tendon-to-bone samples were examined microscopically, histologically, and biomechanically and via micro-computed tomography. All repairs were intact at the time of dissection, with no evidence of gapping or ruptures. Tendon-to-bone healing after repair in our chronic injury model led to reduced bone quality and morphological disorganization at the repair site compared with acute injuries and repair. SS and IS muscles were atrophic at 8 weeks after repair of chronic injuries, indicating incomplete recovery after repair, whereas SS and IS muscles exhibited less atrophy and degeneration in the acute injury group at 8 weeks after repair. After chronic injuries and repair, humeral heads had decreased total mineral density and an altered

  1. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated...... in female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

  2. Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

    Science.gov (United States)

    Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

    2017-06-09

    Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands...... delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined...... administration of synthetic human EGF/URO and cimetidine further increased healing of gastric ulcers compared with administration of each substance. Neither synthetic human EGF/URO, nor removal of the submandibular glands had any influence on gastric acid secretion. This study showed that the submandibular...

  4. Acceleration of vertical migration of corneal epithelial cells in albino rats during chronic immobilization stress

    International Nuclear Information System (INIS)

    Timoshin, S.S.; Berezhnova, N.I.

    1986-01-01

    This paper studies the effect of chronic immobilization stress on the kinetics of corneal epithelial cells from the basal layer into higher layers. Experiments were carried out on 49 male rats. The animals were given an intraperitoneal injection of tritium-thymidine and an additional application of 5 microCi of tritium-thymidine was made to its surface because the cornea has no blood supply. The animals were killed and the cornea removed for investigation. Values of the index of labeled nuclei and intensity of thymidine labeling, characterizing DNA synthesis in the corneas of the control and experimental animals showed no significant change compared with their values in a pervious series of experiments. Chronic exposure to stress increased the velocity of vertical migration of the cells from the basal layer toward the outer layers of the cornea

  5. Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human...... EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more...... human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral...

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  7. Effects of chronic social isolation on Wistar rat behavior and brain plasticity markers.

    Science.gov (United States)

    Djordjevic, Jelena; Djordjevic, Ana; Adzic, Miroslav; Radojcic, Marija B

    2012-01-01

    Chronic stress is a contributing risk factor in the development of psychiatric illnesses, including depressive disorders. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in the brain plasticity. Previously, we investigated the effects of chronic social stress in the limbic brain structures of Wistar rats (hippocampus, HIPPO, and prefrontal cortex, PFC) and found multiple characteristics that resembled alterations described in some clinical studies of depression. We extended our investigations and followed the behavior of stressed animals by the open field test (OFT) and forced swimming test (FST), and the expression and polysialylation of synaptic plasticity markers, neural cell adhesion molecule (NCAM) and L1, in the HIPPO and PFC. We also determined the adrenal gland mass and plasma corticosterone (CORT) as a terminal part of the hypothalamic-pituitary-adrenal axis activity. Our data indicated that stressed animals avoided the central zone in the OFT and displayed decreased swimming, but prolonged immobility in the FST. The animals exhibited marked hypertrophy of the adrenal gland cortex, in spite of decreased serum CORT. Simultaneously, the stressed animals exhibited an increase in NCAM mRNA expression in the HIPPO, but not in the PFC. The synaptosomal NCAM of the HIPPO was markedly polysialylated, while cortical PSA-NCAM was significantly decreased. The results showed that chronic social isolation of Wistar rats causes both anxiety-like and depression-like behavior. These alterations are parallel with molecular changes in the limbic brain, including diminished NCAM sialylation in the PFC. Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology. Copyright © 2012 S. Karger AG, Basel.

  8. Diffusion tensor imaging of spinal cord parenchyma lesion in rat with chronic spinal cord injury.

    Science.gov (United States)

    Zhao, Can; Rao, Jia-Sheng; Pei, Xiao-Jiao; Lei, Jian-Feng; Wang, Zhan-Jing; Zhao, Wen; Wei, Rui-Han; Yang, Zhao-Yang; Li, Xiao-Guang

    2018-04-01

    Adequate evaluation of spinal cord parenchyma and accurate identification of injury range are considered two premises for the research and treatment of chronic spinal cord injury (SCI). Diffusion tensor imaging (DTI) provides information about water diffusion in spinal cord, and thus makes it possible to realize these premises. In this study, we conducted magnetic resonance imaging (MRI) for Wistar rats 84days after spinal cord contusion. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) from different positions of the injured cord were collected, analyzed, and compared with the histological results and locomotor outcomes. Moreover, we performed fiber tractography, and examined the difference in cavity percentage obtained respectively via conventional MRI, DTI and histology. Results showed that the chronic SCI rats had the largest changes of all DTI metrics at the epicenter; the farther away from the epicenter, the smaller the variation. FA, AD and RD were all influenced by SCI in a greater space range than MD. The good consistency of FA values and histological results in specific regions evidenced FA's capability of reflecting Wallerian degeneration after SCI. DTI metrics at the epicenter in ventral funiculus also showed a close correlation with the BBB scores. Additionally, supported by the histological results, DTI enables a more accurate measurement of cavity percentage compared to the conventional MRI. DTI parameters might comprehensively reflect the post-SCI pathological status of spinal cord parenchyma at the epicenter and distal parts during the chronic stage, while showing good consistency with locomotor performance. DTI combined with tractography could intuitively display the distribution of spared fibers after SCI and accurately provide information such as cavity area. This may shed light on the research and treatment of chronic SCI. Copyright © 2017 Elsevier Inc. All rights

  9. Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains.

    Science.gov (United States)

    Abreu, Renata Viana; Silva-Oliveira, Eliane Moretto; Moraes, Márcio Flávio Dutra; Pereira, Grace Schenatto; Moraes-Santos, Tasso

    2011-10-01

    Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive

  10. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    GURPREET KAUR

    2015-03-01

    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  11. Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

    Science.gov (United States)

    Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

    2015-08-01

    One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

  12. Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

    Science.gov (United States)

    Klomp, Anne; Václavů, Lena; Meerhoff, Gideon F; Reneman, Liesbeth; Lucassen, Paul J

    2014-01-01

    The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

  13. Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

    Directory of Open Access Journals (Sweden)

    Anne Klomp

    Full Text Available The antidepressant drug fluoxetine (Prozac has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b effects on tryptophan hydroxylase (TPH expression, a measure of serotonin synthesis; c whether treatment effects during adolescence differed from treatment at an adult age, and d whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+ cells and of the number of young migratory neurons (doublecortin+, revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

  14. Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Bartlomiej Kalaska

    2017-10-01

    Full Text Available The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone

  15. Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation.

    Science.gov (United States)

    Dhahri, Wahiba; Drolet, Marie-Claude; Roussel, Elise; Couet, Jacques; Arsenault, Marie

    2014-09-24

    The composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival. Male Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later. As expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet. HF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.

  16. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    Science.gov (United States)

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.

  17. Chronic hypoxia alters calbindin D-28k immunoreactivity in lingual and laryngeal taste buds in the rat

    OpenAIRE

    Yoshida, T.; Matsuda, H.; Yamamoto, Y.; Hayashida, Y.; Tsukuda, M.; Kusakabe, T.

    2006-01-01

    The distribution and abundance of the calcium binding protein, calbindin D-28k (CB) immunoreactivity in the taste buds of the circumvallate papillae and larynx were compared between normoxic and chronically hypoxic rats (10% O2 for 8 weeks). In the normoxic rats, CB immunoreactivity was observed in some cells and fibers of the intragemmal region of the taste buds in the circumvallate papillae. In contrast, in the subgemmal region of the laryngeal taste buds, fi...

  18. Effects of chronic cesium-137 ingestion on physiological system in rat

    International Nuclear Information System (INIS)

    Voisin, Philippe; Grignard, Elise; Souidi, Maamar; Gueguen, Yann; Lestaevel, Philippe; Grandcolas, Line; Grison, Stephane; Dublineau, Isabelle; Gourmelon, Patrick

    2008-01-01

    Full text: Several diseases have been reported in populations living in contaminated territories in the vicinity of Chernobyl, such as behavior disorders, anxiety symptoms, cardiovascular diseases, perturbations of endocrine and reproductive status, immunity disturbances. Therefore, the post-Chernobyl contamination by 137 Cs is of particular concern for public health. The objective of this study was to determine in a rat model the effects of 137 Cs contamination by ingestion of 6500 Bq/L on several physiological systems, central nervous system, cardiovascular system, steroidogenesis, intestinal functions, metabolism of cholesterol and of vitamin D. The animals were chronically and sub-chronically contaminated via drinking water (∼150 Bq per day) at a post-accidental dose level. Our experiments demonstrated that chronic ingestion of 137 Cs induced some disturbances of these systems. A decrease in blood pressure was observed in contaminated animals. At the same time, changes in cardiac function were evidenced via increased plasma levels of CK and CK-MB and variations in gene expression of proteins involved in vascular tonus (Gueguen et al. Toxicol Lett 2007), and of K + channels in cardiac left ventricle. Vitamin D metabolism was also modified by 137 Cs with a diminution of plasma level of Vitamin D (1,25(OH)D3), and changes in mRNA levels of cytochrome P450 CYP27B1 and CYP2R1 in brain and liver (Tissandie et al. Toxicology 2006). Concerning cholesterol metabolism, no changes in plasma lipid levels were noted, although increased gene expression of liver X receptor α (LXRα), low-density lipoprotein receptor (LDLr) and apolipoprotein B (ApoB) (Souidi et al. Int J Toxicol 2006). In addition, steroidogenesis seemed to be modified, since decreased plasma level of 17β-estradiol and increased corticosterone plasma level were observed following chronic 137 Cs ingestion. These changes were associated with modification of mRNA levels of nuclear receptors in testis and of

  19. Chronic effects of cesium-137 ingestion on physiological systems in rat

    International Nuclear Information System (INIS)

    Voisin, Philippe; Grignard, Elise; Souidi, Maamar; Gueguen, Yann; Lestaevel, Philippe; Grandcolas, Line; Grison, Stephane; Dublineau, Isabelle; Gourmelon, Patrick

    2008-01-01

    Full text: The post-Chernobyl contamination by cesium-137 is of particular concern for public health. Several diseases have been reported in populations living in contaminated territories, such as behavior disorders, anxiety symptoms, cardiovascular diseases, perturbations of endocrine and reproductive status, immunity disturbances. The objective of this study was to determine in a rat model the effects of 137 Cs contamination by ingestion of post-accidental dose (6500 Bq/L) on several physiological systems, central nervous system, cardiovascular system, steroidogenesis, intestinal functions, and metabolism of cholesterol and of vitamin D. The animals were chronically and sub chronically contaminated via drinking water (∼150Bq per day). These experiments demonstrated that chronic ingestion of 137 Cs induced modifications of these physiological systems. A decrease in blood pressure was observed in contaminated animals. At the same time, changes in cardiac function were evidenced via increased plasma levels of CK and CK-MB and variations in gene expression of proteins involved in vascular tonus and of K + channels in cardiac left ventricle. Vitamin D metabolism was also modified by 137 Cs with a diminution of plasma level of Vitamin D (1,25(OH)D3), and changes in mRNA levels of cytochrome P450 CYP27B1 and CYP2R1 in brain and liver. Concerning cholesterol metabolism, no changes in plasma lipid levels were noted, although increased gene expression of liver X receptor α (LXRα), low-density lipoprotein receptor (LDLr) and apolipoprotein B (ApoB). In addition, steroidogenesis seemed to be modified, since decreased plasma level of 17β-estradiol and increased corticosterone plasma level were observed following chronic 137 Cs ingestion. These changes were associated with modification of mRNA levels of nuclear receptors in testis and of cytochrome P450 CYP11a1 in adrenal. Evaluation of intestine function demonstrated few effects of 137 Cs after chronic ingestion, except

  20. N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity.

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    Leonardo Victor Barbosa Pereira

    Full Text Available The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC. Male Wistar rats were submitted to 5/6 nephrectomy (Nx to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine was administrated (1.5 mM/KgBW, intravenously 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7; 2--Nx+NAC (n = 6; 3--Nx+Gd (n = 7; 4--Nx+NAC+Gd (4.8 g/L in drinking water, initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6. This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW, proteinuria (mg/24 hs, serum iron (µg/dL; serum ferritin (ng/mL; transferrin saturation (%, TIBC (µg/dL and TBARS (nmles/ml. Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

  1. Chronic treatment with repetitive transcranial magnetic stimulation inhibits seizure induction by electroconvulsive shock in rats.

    Science.gov (United States)

    Fleischmann, A; Hirschmann, S; Dolberg, O T; Dannon, P N; Grunhaus, L

    1999-03-15

    Studies in laboratory animals suggest that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive shock (ECS) increase seizure inhibition acutely. This study was designed to explore whether chronic rTMS would also have seizure inhibition properties. To this purpose we administered rTMS (Magstim Rapid) and sham rTMS twice daily (2.5 T, 4-sec train duration, 20 Hz) to two groups of 10 rats for 16 days. The rTMS coil was a 50-mm figure-8 coil held directly over the rat's head. Raters were blind to experimental groups. On days 11, 17, and 21 (5 days after the last rTMS) ECS was administered with a Siemens convulsator using three electrical charge levels. Variables examined were the presence or absence of seizures and seizure length (measured from the initiation of the tonic contraction until the end of the limb movement). At day 11 rTMS had no effect on seizures, and both rTMS and sham rTMS animals convulsed equally. At day 17, however, rTMS-treated animals convulsed significantly less (both at presence/absence of seizures, and at seizure length) than sham rTMS animals. At day 21 the effects of rTMS had disappeared. These findings suggest that rTMS administered chronically leads to changes in seizure threshold similar to those reported for ECS and ECT; however, these effects were short-lived.

  2. Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats.

    Science.gov (United States)

    Soellner, Deborah E; Grandys, Theresa; Nuñez, Joseph L

    2009-12-14

    In this report, we demonstrate that chronic prenatal exposure to a moderate dose of caffeine disrupts novel object recognition and radial arm maze behaviors in adult male and female rats. Pregnant dams were administered either tap water or 75 mg/L caffeinated tap water throughout gestation. Oral self-administration in the drinking water led to an approximate maternal intake of 10mg/kg/day, equivalent to 2-3 cups of coffee/day in humans based on a metabolic body weight conversion. In adulthood, the offspring underwent testing on novel object recognition, radial arm maze, and Morris water maze tasks. Prenatal caffeine exposure was found to impair 24-h memory retention in the novel object recognition task and impair both working and reference memory in the radial arm maze. However, prenatal caffeine exposure did not alter Morris water maze performance in either a simple water maze procedure or in an advanced water maze procedure that included reversal and working memory paradigms. These findings demonstrate that chronic oral intake of caffeine throughout gestation can alter adult cognitive behaviors in rats.

  3. Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium.

    Science.gov (United States)

    Rouas, Caroline; Stefani, Johanna; Grison, Stéphane; Grandcolas, Line; Baudelin, Cédric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

    2011-01-11

    Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium

    International Nuclear Information System (INIS)

    Rouas, Caroline; Stefani, Johanna; Grison, Stephane; Grandcolas, Line; Baudelin, Cedric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

    2011-01-01

    Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant.

  5. Effects of chronic alternating cadmium exposure on the episodic secretion of prolactin in male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Madrid Univ. (Spain). Facultad de Medicina Complutense; Marquez, N.; Alvarez-Demanuel, E.; Lafuente, A. [Vigo Univ., Orense (Spain). Lab. de Toxicologia

    1998-07-01

    Cadmium increases or decreases prolactin secretion depending on the dose and duration of the exposure to the metal. However, whether there are cadmium effects on the episodic prolactin secretion is less well known. This study was undertaken to address whether chronic alternating exposure to two different doses of cadmium affects the episodic pattern of prolactin and to what extent the effects of cadmium are age-dependent. Male rats were treated s.c. with cadmium chloride (0.5 or 1.0 mg/kg) from day 30 to 60, or from day 60 to 90 of age, with alteration of the doses every 4 days, starting with the smaller dose. Controls received vehicle every 4 days. The last dose of cadmium was given 48 h prior to the pulsatility study. Prolactin secretion in the 4 experimental groups studied was episodic and changed significantly after cadmium exposure. Cadmium administration from day 30 to 60 of life significantly decreased the mean half-life of prolactin. On the other hand, when administered from day 60 to 90 cadmium significantly decreased the mean as well as serum prolactin levels and the absolute amplitude of the prolactin pulses, their duration, the relative amplitude or the mean half-life of the hormone. The frequency of prolactin peaks was not changed by cadmium administration. The results indicate that low intermittent doses of cadmium chronically administered change the episodic secretion pattern of prolactin in rats. The effects of cadmium on prolactin secretion were age dependent. (orig.)

  6. PA21, a novel phosphate binder, improves renal osteodystrophy in rats with chronic renal failure.

    Science.gov (United States)

    Yaguchi, Atsushi; Tatemichi, Satoshi; Takeda, Hiroo; Kobayashi, Mamoru

    2017-01-01

    The effects of PA21, a novel iron-based and non-calcium-based phosphate binder, on hyperphosphatemia and its accompanying bone abnormality in chronic kidney disease-mineral and bone disorder (CKD-MBD) were evaluated. Rats with adenine-induced chronic renal failure (CRF) were prepared by feeding them an adenine-containing diet for four weeks. They were also freely fed a diet that contained PA21 (0.5, 1.5, and 5%), sevelamer hydrochloride (0.6 and 2%) or lanthanum carbonate hydrate (0.6 and 2%) for four weeks. Blood biochemical parameters were measured and bone histomorphometry was performed for femurs, which were isolated after drug treatment. Serum phosphorus and parathyroid hormone (PTH) levels were higher in the CRF rats. Administration of phosphate binders for four weeks decreased serum phosphorus and PTH levels in a dose-dependent manner and there were significant decreases in the AUC0-28 day of these parameters in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups compared with that in the CRF control group. Moreover, osteoid volume improved significantly in 5% of the PA21 group, and fibrosis volume and cortical porosity were ameliorated in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups. These results suggest that PA21 is effective against hyperphosphatemia, secondary hyperparathyroidism, and bone abnormalities in CKD-MBD as sevelamer hydrochloride and lanthanum carbonate hydrate are, and that PA21 is a new potential alternative to phosphate binders.

  7. Neo-Timm staining in the thalamus of chronically epileptic rats

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    Hamani C.

    2005-01-01

    Full Text Available The thalamus is an important modulator of seizures and is severely affected in cholinergic models of epilepsy. In the present study, chronically epileptic rats had their brains processed for neo-Timm and acetylcholinesterase two months after the induction of status epilepticus with pilocarpine. Both controls and pilocarpine-treated animals presented neo-Timm staining in the anterodorsal nucleus, laterodorsal nucleus, reticular nucleus, most intralaminar nuclei, nucleus reuniens, and rhomboid nucleus of the thalamus, as well as in the zona incerta. The intensity of neo-Timm staining was similar in control and pilocarpine-treated rats, except for the nucleus reuniens and the rhomboid nucleus, which had a lower intensity of staining in the epileptic group. In animal models of temporal lobe epilepsy, zinc seems to modulate glutamate release and to decrease seizure activity. In this context, a reduction of neo-Timm-stained terminals in the midline thalamus could ultimately result in an increased excitatory activity, not only within its related nuclei, but also in anatomical structures that receive their efferent connections. This might contribute to the pathological substrate observed in chronic pilocarpine-treated epileptic animals.

  8. Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

    Science.gov (United States)

    Kamal, Amer; Van der Harst, Johanneke E; Kapteijn, Chantal M; Baars, Annemarie J M; Spruijt, Berry M; Ramakers, Geert M J

    2010-04-01

    Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

  9. [Sodium hydrosulfide improves cardiac functions and structures in rats with chronic heart failure].

    Science.gov (United States)

    Li, Xiao-hui; Zhang, Chao-ying; Zhang, Ting

    2011-11-22

    To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling. A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared. At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed an amelioration of myocardial damage, an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-I collagen). Compared with the sham operation and shunt + NaHS groups, the shunt group displayed increased right ventricular hydroxyproline (mg×g(-1)·pro: 1.32 ± 0.25 vs 0.89 ± 0.18 and 0.83 ± 0.19, all P < 0

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

    Science.gov (United States)

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

    2017-06-03

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

  11. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

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    Amira M. Abo-youssef

    2016-06-01

    Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

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

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    Claudia Daniela Montes-Angeles

    2017-10-01

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

  13. Mechanism of potassium depletion during chronic metabolic acidosis in the rat

    International Nuclear Information System (INIS)

    Scandling, J.D.; Ornt, D.B.

    1987-01-01

    Pair-fed rats on a normal K diet were given either 1.5% NH 4 Cl or water for 4 days. The acid-fed animals developed metabolic acidosis, negative K balance, and K depletion. Urinary Na excretion and urinary flow were not different between the groups beyond the first day. After the 4 days, isolated kidneys from animals in each of these groups were perfused at normal pH and bicarbonate concentrations. Urinary K excretion was similar between the groups despite the potassium depletion in the acid-fed animals. In contrast, isolated kidneys from animals with comparable K depletion induced by dietary K restriction readily conserved K. Sodium excretion and urinary flow were similar among the three groups of isolated kidneys. Plasma aldosterone concentrations were greater in the acid-fed rats after the 4 days of NH 4 Cl ingestion than in the control animals. Adrenalectomized rats were treated with either normal (4 μg/day) or high (22 μg/day) aldosterone replacement while ingesting NH 4 Cl for 4 days. Only in the presence of high aldosterone replacement did the acid-fed adrenalectomized animals develop K depletion. The authors conclude that chronic metabolic acidosis stimulates aldosterone secretion, and that aldosterone maintains the inappropriately high urinary potassium excretion and K depletion seen in this acid-base disorder

  14. Chronic consumption of trans fat can facilitate the development of hyperactive behavior in rats.

    Science.gov (United States)

    Pase, C S; Roversi, Kr; Trevizol, F; Kuhn, F T; Dias, V T; Roversi, K; Vey, L T; Antoniazzi, C T; Barcelos, R C S; Bürger, M E

    2015-02-01

    In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Oral exposure to dibutyl phthalate exacerbates chronic lymphocytic thyroiditis through oxidative stress in female Wistar rats.

    Science.gov (United States)

    Wu, Yang; Li, Jinquan; Yan, Biao; Zhu, Yuqing; Liu, Xudong; Chen, Mingqing; Li, Dai; Lee, Ching-Chang; Yang, Xu; Ma, Ping

    2017-11-13

    Chronic lymphocytic thyroiditis (CLT) is a common autoimmune disorder. The possible pathogenic role and mechanism of dibutyl phthalate (DBP) in CLT is still controversial. Experiments were conducted after 35-days of oral exposure to the three concentrations of DBP or saline, and three immunizations with thyroglobulin (TG). Healthy female Wistar rats were randomly divided into ten exposure groups (n = 8 each): (A) saline control, (B) 0.5 mg/kg/d DBP, (C) 5 mg/kg/d DBP, (D) 50 mg/kg/d DBP, (E) TG-immunized group, (F) TG- combined with 0.5 mg/kg/d DBP, (G) TG- combined with 5 mg/kg/d DBP, (H) TG- combined with 50 mg/kg/d DBP, (I) TG- combined with 50 mg/kg/d DBP plus 100 mg/kg/d vitamin C; (J) 100 mg/kg/d vitamin C. We showed that oral exposure DBP can aggravate CLT in rats. This deterioration was concomitant with increased thyroid auto antibodies, Th1/Th2 imbalance and Th17 immune response, activated pro-inflammatory and apoptosis pathways, and increased thyroid dysfunction in rats. Our results also suggested that DBP could promote oxidative damage. The study also found that vitamin C reduced the levels of oxidative stress and alleviated CLT. In short, the study showed that DBP exacerbated CLT through oxidative stress.

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

    International Nuclear Information System (INIS)

    Okoh, P.N.

    1983-01-01

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

  17. Chronic restraint stress induces sperm acrosome reaction and changes in testicular tyrosine phosphorylated proteins in rats

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    Supatcharee Arun

    2016-07-01

    Full Text Available Background: Stress is a cause of male infertility. Although sex hormones and sperm quality have been shown to be low in stress, sperm physiology and testicular functional proteins, such as phosphotyrosine proteins, have not been documented. Objective: To investigate the acrosome status and alterations of testicular proteins involved in spermatogenesis and testosterone synthesis in chronic stress in rats. Materials and Methods: In this experimental study, male rats were divided into 2 groups (control and chronic stress (CS, n=7. CS rats were immobilized (4 hr/day for 42 consecutive days. The blood glucose level (BGL, corticosterone, testosterone, acrosome status, and histopathology were examined. The expressions of testicular steroidogenic acute regulatory (StAR, cytochrome P450 side chain cleavage (CYP11A1, and phosphorylated proteins were analyzed. Results: Results showed that BGL (71.25±2.22 vs. 95.60±3.36 mg/dl, corticosterone level (24.33±4.23 vs. 36.9±2.01 ng/ml, acrosome reacted sperm (3.25±1.55 vs. 17.71±5.03%, and sperm head abnormality (3.29±0.71 vs. 6.21±1.18% were significantly higher in CS group in comparison with control. In contrast, seminal vesicle (0.41±0.05 vs. 0.24±0.07 g/100g, testosterone level (3.37±0.79 vs. 0.61±0.29 ng/ml, and sperm concentration (115.33±7.70 vs. 79.13±3.65×106 cells/ml of CS were significantly lower (p<0.05 than controls. Some atrophic seminiferous tubules and low sperm mass were apparent in CS rats. The expression of CYP11A1 except StAR protein was markedly decreased in CS rats. In contrast, a 55 kDa phosphorylated protein was higher in CS testes. Conclusion: CS decreased the expression of CYP11A, resulting in decreased testosterone, and increased acrosome-reacted sperm, assumed to be the result of an increase of 55 kDa phosphorylated protein.

  18. H,K-ATPase and carbonic anhydrase response to chronic systemic rat gastric hypoxia

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    Ulfah Lutfiah

    2015-11-01

    Full Text Available Background: Hypoxia may induce gastric ulcer associated with excessive hidrogen chloride (HCl secretion. Synthesis of HCl involves 2 enzymes, H,K-ATPase and carbonic anhydrase (CA. This study aimed to clarify the underlying cause of gastric ulcer in chronic hypoxic condition, by investigating the H,K-ATPase and CA9 response in rats.Methods: This study was an in vivo experiment, to know the relationship between hypoxia to expression of H,K-ATPase and CA9 mRNA, and H,K-ATPase and total CA specific activity of chronic systemic rat gastric hypoxia. The result was compared to control. Data was analyzed by SPSS. If the data distribution was normal and homogeneous, ANOVA and LSD post-hoc test were used. However, if the distribution was not normal and not homogeneous, and still as such after transformation, data was treated in non-parametric using Kruskal-Wallis and Mann Whitney test. Twenty five male Sprague-Dawley rats were divided into 5 groups: rats undergoing hypoxia for 1, 3, 5, and 7 days placed in hypoxia chamber (10% O2, 90% N2, and one control group. Following this treatment, stomach of the rats was extracted and homogenized. Expression of H,K-ATPase and CA9 mRNA was measured using real time RT-PCR. Specific activity of H,K-ATPase was measured using phosphate standard solution, and specific activity of total CA was measured using p-nitrophenol solution.Results: The expression of H,K-ATPase mRNA was higher in the first day (2.159, and drastically lowered from the third to seventh day (0.289; 0.108; 0.062. Specific activities of H,K-ATPase was slightly higher in the first day (0.765, then was lowered in the third (0.685 and fifth day (0.655, and was higher in the seventh day (0.884. The expression of CA9 mRNA was lowered progressively from the first to seventh day (0.84; 0.766; 0.736; 0.343. Specific activities of total CA was low in the first day (0.083, and was higher from the third to seventh day (0.111; 0.136; 0.144.Conclusion: In hypoxia

  19. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

    Energy Technology Data Exchange (ETDEWEB)

    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak [University of Ljubljana, Department of Biology, Biotechnical Faculty (Slovenia); Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd, E-mail: gorazd.drevensek@mf.uni-lj.si [University of Ljubljana, Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine (Slovenia)

    2016-10-15

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes (n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  20. Effect of chronic fish oil supplementation on renal function of normal and cachectic rats

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    R. Fernandez

    2004-10-01

    Full Text Available In the present study we determined the effect of chronic diet supplementation with n-3 PUFA on renal function of healthy and cachectic subjects by providing fish oil (1 g/kg body weight to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined its effect on renal function parameters during their adulthood. The animals were divided into four groups of 5-10 rats in each group: control, control supplemented with fish oil (P, cachectic Walker 256 tumor-bearing (W, and W supplemented with fish oil (WP. Food intake was significantly lower in the W group compared to control (12.66 ± 4.24 vs 25.30 ± 1.07 g/day. Treatment with fish oil significantly reversed this reduction (22.70 ± 2.94 g/day. Tumor growth rate was markedly reduced in the P group (16.41 ± 2.09 for WP vs 24.06 ± 2.64 g for W. WP group showed a significant increase in mean glomerular filtration rate compared to P and control (1.520 ± 0.214 ml min-1 kg body weight-1; P < 0.05. Tumor-bearing groups had low urine osmolality compared to control rats. The fractional sodium excretion decreased in the W group compared to control (0.43 ± 0.16 vs 2.99 ± 0.87%; P < 0.05, and partially recovered in the WP group (0.90 ± 0.20%. In summary, the chronic supplementation with fish oil used in this study increased the amount of fat in the diet by only 0.1%, but caused remarkable changes in tumor growth rate and cachexia, also showing a renoprotective function.

  1. Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

    Science.gov (United States)

    Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

    2017-08-01

    Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Effect of chronic treatment with a cyclooxygenase inhibitor on reproductive parameters in male rat

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    Saeed, S.A.; Anwar, N.; Khan, K.M.; Sarfraz, N.

    2009-01-01

    Indomethacin is a member of non-steroidal anti-inflammatory drugs (NSAIDs) commonly used for treatment of gout, arthritis, and other inflammatory conditions. It has been shown to inhibit ovarian prostaglandins synthesis in mammals, birds, fish and reptiles. However, the effects of its chronic administration on male reproductive functions remain largely unknown. Using rat as a model, we studied the effect of chronic treatment with indomethacin on the male reproductive system. Methods: Testosterone was measured in the serum, testicular tissue, and testicular interstitial fluid by radioimmunoassay. Moreover, we also studied the direct effect of indomethacin in vitro on luteinizing hormone stimulated testosterone secretion from the Leydig cells isolated from various treatment groups. Results: Indomethacin treatment for 50 days caused a significant but reversible decrease in prostate weight, epididymal sperm reserves and sperm motility score compared with control rats (p<0.05). In vitro stimulation of Leydig cells isolated from treated rat's testes with luteinizing hormone (250 mu IU) produced significantly reduced testosterone compared with cells from control groups (p<0.05). Furthermore, stimulatory effect of luteinizing hormone on the control Leydig cells was significantly reduced when these cells were challenged with luteinizing hormone in the presence of indomethacin, (p<0.05). Testosterone concentration in the testicular tissue and testicular interstitial fluid reduced after indomethacin treatment (p<0.05). Conclusion: Due to its significant inhibition of key reproductive hormones, indomethacin effectively inhibits reproductive functions if used on a long-term basis. In his study, we have identified potential risks in the long-term use of cyclooxygenase inhibitors. (author)

  3. Comparative experimental evaluation of the efficacy of Prostamol Uno and Samprost on rat model of chronic aseptic prostate inflammation.

    Science.gov (United States)

    Pahomova, A V; Borovskaja, T G; Fomina, T I; Ermolaeva, L A; Vychuzhanina, A V; Rumpel, O A; Granstrem, O K; Baranova, O V

    2011-11-01

    Comparative experimental evaluation of the efficiency of prostatotropic drugs Prostamol Uno and Samprost on the model of the chronic aseptic prostate inflammation in rats was performed. It was established that peptide drug Samprost decelerates sclerotic processes in the prostate gland to a greater extent than herbal preparation Prostamol Uno. Both products equally stimulate secretory activity of the gland. Prostamol Uno, unlike Samprost, prevents the development of reduced sexual motivation, one of the complications of chronic prostatitis.

  4. Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.

    Science.gov (United States)

    Dina, Olayinka A; Joseph, Elizabeth K; Levine, Jon D; Green, Paul G

    2010-04-01

    While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. Copyright 2010 American Pain Society. All rights reserved.

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

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    Masoumeh Emamghoreishi

    2015-02-01

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

  6. Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats.

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    Hila Abush

    Full Text Available The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg for two weeks during the late adolescence period (post-natal days 45-60 and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP in the ventral subiculum (vSub-nucleus accumbens (NAc pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

  7. Vitamin C and E chronic supplementation differentially affect hepatic insulin signaling in rats.

    Science.gov (United States)

    Ali, Mennatallah A; Eid, Rania M H M; Hanafi, Mervat Y

    2018-02-01

    Vitamin C and vitamin E supplementations and their beneficial effects on type 2 diabetes mellitus (T2DM) have been subjected to countless controversial data. Hence, our aim is to investigate the hepatic molecular mechanisms of any diabetic predisposing risk of the chronic administration of different doses of vitamin E or vitamin C in rats. The rats were supplemented with different doses of vitamin C or vitamin E for eight months. Vitamin C and vitamin E increased fasting blood glucose, insulin, and homeostasis model assessment index for insulin resistance (HOMA). Vitamin C disrupted glucose tolerance by attenuating upstream hepatic insulin action through impairing the phosphorylation and activation of insulin receptor and its subsequent substrates; however, vitamin E showed its effect downstream insulin receptor in the insulin signaling pathway, reducing hepatic glucose transporter-2 (GLUT2) and phosphorylated protein kinase (p-Akt). Moreover, both vitamins showed their antioxidant capabilities [nuclear factor-erythroid-2-related factor 2 (Nrf2), total and reduced glutathione] and their negative effect on Wnt pathway [phosphorylated glycogen synthase kinase-3β (p-GSK-3β)], by altering the previously mentioned parameters, inevitably leading to severe reduction of reactive oxygen species (ROS) below the physiological levels. In conclusion, a detrimental effect of chronic antioxidant vitamins supplementation was detected; leading to insulin resistance and impaired glucose tolerance obviously through different mechanisms. Overall, these findings indicate that the conventional view that vitamins promote health benefits and delay chronic illnesses and aging should be modified or applied with caution. Copyright © 2017. Published by Elsevier Inc.

  8. Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats.

    Science.gov (United States)

    Shankar, Priyanka; Ghosh, Sudip; Bhaskarachary, K; Venkaiah, K; Khandare, Arjun L

    2013-07-14

    The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F - ; low-Ca (0·25 %) diet (LCD), Ca - F - ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca - F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca - F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca - F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca - F - and Ca - F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca - F+/Ca+F - and Ca - F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca - F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.

  9. Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

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    Duo-Yi Li

    2015-01-01

    Full Text Available Background: Pulsed radiofrequency (PRF application to the dorsal root ganglia can reduce neuropathic pain (NP in animal models, but the effect of PRF on damaged peripheral nerves has not been examined. We investigated the effect of PRF to the rat sciatic nerve (SN on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI. Methods: The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT and thermal withdrawal latency (TWL. Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group. The contralateral SN served as a control. The MWT and TWL were determined again 2, 4, 6, 8, 10, 12, and 14 days after the PRF or sham treatment. On day 14, ipsilateral and contralateral common SNs were excised and examined by electron microscopy. Results: Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P = 0.000. In the PRF group, MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P = 0.000, while no such difference was observed in the sham group (P > 0.05. Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group. Conclusions: Hyperalgesia is relieved, and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP.

  10. Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat.

    Science.gov (United States)

    Gozal, D; Daniel, J M; Dohanich, G P

    2001-04-01

    The role played by chronic episodic hypoxia (EHYP) in the neurocognitive morbidity of obstructive sleep apnea (OSA) is unknown. Sleep recordings, Morris water maze experiments, and immunohistochemistry for NMDA NR1 glutamate receptor, c-fos protein, and apoptosis [nuclear immunoreactivity for single-stranded DNA and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay] were conducted in EHYP-exposed Sprague Dawley male rats. Exposures consisted of up to14 d in an environmental chamber in which O(2) concentrations were cycled between 10 and 21% every 90 sec or 30 min during 12 hr of daylight. For the remaining 12 hr, EHYP rats breathed room air, while controls spent 14 d in room air. Although EHYP induced significant disruption of sleep architecture during the initial day of exposure, sleep patterns normalized thereafter. Marked increases in apoptosis occurred in the CA1 hippocampal region (sevenfold) and cortex (Cx; eightfold) after 1-2 d of EHYP but not in CA3 and were followed by decreases toward normoxic levels by 14 d. Double labeling for NMDA NR1 and c-fos revealed marked architectural disorganization in CA1 and Cx with increases in c-fos over time. Rats exposed to EHYP displayed significantly longer escape latencies and swim path lengths to escape a hidden platform during 12 training trials given over 2 d. Differences in the performances of EHYP and control rats, although reduced, persisted after 14 d of recovery. We conclude that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions. Furthermore, EHYP impaired performance during acquisition of a cognitive spatial task without affecting sensorimotor function. Such changes may underlie components of the learning and memory impairments found in OSA.

  11. Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial

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    Deise M. Pacheco

    2016-01-01

    Full Text Available ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF following myocardial infarction. Method Twenty-seven male adult Wistar rats were randomized to CHF group (n=12 or Sham group (n=15. Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. Results The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs and the total lung capacity (TLC were lower (40% and 27%, respectively in the CHF rats when compared to the Sham group (P<0.01. There was also an increase in tissue resistance (Gti and elastance (Hti (28% and 45%, respectively in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01, while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02 in the CHF group when compared to the control. Pearson’s correlation coefficient showed a negative association between pulmonary edema and Crs (r=–0.70, P=0.0001 and between pulmonary edema and TLC (r=–0.67,P=0.0034. Pulmonary edema correlated positively with Gti (r=0.68, P=0.001 and Hti (r=0.68, P=0.001. Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001. Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions.

  12. Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

    Science.gov (United States)

    Li, Duo-Yi; Meng, Lan; Ji, Nan; Luo, Fang

    2015-01-01

    Background: Pulsed radiofrequency (PRF) application to the dorsal root ganglia can reduce neuropathic pain (NP) in animal models, but the effect of PRF on damaged peripheral nerves has not been examined. We investigated the effect of PRF to the rat sciatic nerve (SN) on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI). Methods: The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group. The contralateral SN served as a control. The MWT and TWL were determined again 2, 4, 6, 8, 10, 12, and 14 days after the PRF or sham treatment. On day 14, ipsilateral and contralateral common SNs were excised and examined by electron microscopy. Results: Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P = 0.000). In the PRF group, MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P = 0.000), while no such difference was observed in the sham group (P > 0.05). Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group. Conclusions: Hyperalgesia is relieved, and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP. PMID:25673460

  13. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

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    Chung-Kan Peng

    Full Text Available Lung ischemia reperfusion injury (LIRI is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75% diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS, proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF. The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

  14. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

    International Nuclear Information System (INIS)

    Balaha, Mohamed; Kandeel, Samah; Barakat, Waleed

    2016-01-01

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL 4 in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL 4 induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis in chronic

  15. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

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    Balaha, Mohamed, E-mail: Mohamed.Balaha@Med.Tanta.Edu.Eg [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Kandeel, Samah [Histology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Barakat, Waleed [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt)

    2016-11-15

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL{sub 4} in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL{sub 4} induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis

  16. Chronological changes in astrocytes induced by chronic electrical sensorimotor cortex stimulation in rats.

    Science.gov (United States)

    Morishita, Takashi; Yamashita, Akiko; Katayama, Yoichi; Oshima, Hideki; Nishizaki, Yuji; Shijo, Katsunori; Fukaya, Chikashi; Yamamoto, Takamitsu

    2011-01-01

    Motor cortex stimulation (MCS) is a treatment option for various disorders such as medically refractory pain, poststroke hemiplegia, and movement disorders. However, the exact mechanisms underlying its effects remain unknown. In this study, the effects of long-term chronic MCS were investigated by observing changes in astrocytes. A quadripolar stimulation electrode was implanted on the dura over the sensorimotor cortex of adult rats, and the cortex was continuously stimulated for 3 hours, 1 week, 4 weeks, and 8 weeks. Immunohistochemical staining of microglia (ionized calcium-binding adaptor molecule 1 [Iba1] staining) and astrocytes (glial fibrillary acidic protein [GFAP] staining), and neuronal degeneration histochemistry (Fluoro-Jade B staining) were carried out to investigate the morphological changes following long-term chronic MCS. Iba1 staining and Fluoro-Jade B staining showed no evidence of Iba1-positive microglial changes or neurodegeneration. Following continuous MCS, GFAP-positive astrocytes were enlarged and their number increased in the cortex and the thalamus of the stimulated hemisphere. These findings indicate that chronic electrical stimulation can continuously activate astrocytes and result in morphological and quantitative changes. These changes may be involved in the mechanisms underlying the neuroplasticity effect induced by MCS.

  17. Exercise Ameliorates Endocrine Pancreas Damage Induced by Chronic Cola Drinking in Rats.

    Directory of Open Access Journals (Sweden)

    Matilde Otero-Losada

    Full Text Available This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats.Forty-eight Wistar rats were randomly assigned to 4 groups depending on a beverage consumption ad libitum, water (W or cola beverage (C, and b physical activity, sedentary (S or treadmill running (R. Accordingly, 4 groups were studied: WS (water sedentary, WR (water runner, CS (cola sedentary and CR (cola runner. Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry, and systolic blood pressure (plethysmography were measured. After 6 months, euthanasia was performed (overdose sodium thiopental. Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations.The effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001 rather than simple summation. Cola drinking (CS vs WS reduced median pancreatic islet area (-30%, 1.8 104 μm2 vs 2.58 104 μm2, p<0.0001 and median β-cell mass (-43%, 3.81 mg vs 6.73 mg, p<0.0001, and increased median α/β ratio (+49%, 0.64 vs 0.43, p< 0.001. In water drinking rats (WR vs WS, running reduced median α-cell mass (-48%, 1.48 mg vs 2.82 mg, p<0.001 and α/β ratio (-56%, 0.19 vs 0.43, p<0.0001. Differently, in cola drinking rats (CR vs CS, running partially restored median islet area (+15%, 2.06 104 μm2 vs 1.79 104 μm2, p<0.05, increased median β-cell mass (+47%, 5.59 mg vs 3.81 mg, p <0.0001 and reduced median α/β ratio (-6%, 0.60 vs 0.64, p<0.05.This study is likely the first reporting experimental evidence of the beneficial effect of exercise on pancreatic morphology in cola-drinking rats. Presently, the increase of nearly 50% in β cells mass by running in cola drinking rats is by far the most relevant finding. Moderate running, advisably indicated in cola consumers and

  18. Cardiovascular and metabolic consequences of the association between chronic stress and high-fat diet in rats.

    Science.gov (United States)

    Simas, Bruna B; Nunes, Everson A; Crestani, Carlos C; Speretta, Guilherme F

    2018-05-01

    Obesity and chronic stress are considered independent risk factors for the development of cardiovascular diseases and changes in autonomic system activity. However, the cardiovascular consequences induced by the association between high-fat diet (HFD) and chronic stress are not fully understood. We hypothesized that the association between HFD and exposure to a chronic variable stress (CVS) protocol for four weeks might exacerbate the cardiovascular and metabolic disturbances in rats when compared to these factors singly. To test this hypothesis, male Wistar rats were divided into four groups: control-standard chow diet (SD; n = 8); control-HFD (n = 8); CVS-SD (n = 8); and CVS-HFD (n = 8). The CVS consisted of repeated exposure of the rats to different inescapable and unpredictable stressors (restraint tress; damp sawdust, cold, swim stress and light cycle inversion). We evaluated cardiovascular function, autonomic activity, dietary intake, adiposity and metabolism. The HFD increased body weight, adiposity and blood glucose concentration (∼15%) in both control and CVS rats. The CVS-HFD rats showed decreased insulin sensitivity (25%) compared to CVS-SD rats. The control-HFD and CVS-HFD rats presented increased intrinsic heart rate (HR) values (∼8%). CVS increased cardiac sympathetic activity (∼65%) in both SD- and HFD-fed rats. The HFD increased basal HR (∼10%). Blood pressure and baroreflex analyzes showed no differences among the experimental groups. In conclusion, the present data indicate absence of interaction on autonomic imbalance evoked by either CVS or HFD. Additionally, HFD increased HR and evoked metabolic disruptions which are independent of stress exposure.

  19. Acute versus chronic phase mechanisms in a rat model of CRPS.

    Science.gov (United States)

    Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

    2016-01-19

    Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4

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

    Science.gov (United States)

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

  1. Exercise training attenuated chronic cigarette smoking-induced up-regulation of FIZZ1/RELMα in lung of rats.

    Science.gov (United States)

    Ma, Wan-li; Cai, Peng-cheng; Xiong, Xian-zhi; Ye, Hong

    2013-02-01

    FIZZ/RELM is a new gene family named "found in inflammatory zone" (FIZZ) or "resistin-like molecule" (RELM). FIZZ1/RELMα is specifically expressed in lung tissue and associated with pulmonary inflammation. Chronic cigarette smoking up-regulates FIZZ1/RELMα expression in rat lung tissues, the mechanism of which is related to cigarette smoking-induced airway hyperresponsiveness. To investigate the effect of exercise training on chronic cigarette smoking-induced airway hyperresponsiveness and up-regulation of FIZZ1/RELMα, rat chronic cigarette smoking model was established. The rats were treated with regular exercise training and their airway responsiveness was measured. Hematoxylin and eosin (HE) staining, immunohistochemistry and in situ hybridization of lung tissues were performed to detect the expression of FIZZ1/RELMα. Results revealed that proper exercise training decreased airway hyperresponsiveness and pulmonary inflammation in rat chronic cigarette smoking model. Cigarette smoking increased the mRNA and protein levels of FIZZ1/RELMα, which were reversed by the proper exercise. It is concluded that proper exercise training prevents up-regulation of FIZZ1/RELMα induced by cigarette smoking, which may be involved in the mechanism of proper exercise training modulating airway hyperresponsiveness.

  2. BENEFICIAL EFFECT OF CHRONIC NIMODIPINE TREATMENT ON BEHAVIORAL DYSFUNCTIONS OF AGED RATS EXPOSED TO PERINATAL ETHANOL TREATMENT

    NARCIS (Netherlands)

    MARKEL, E; FELSZEGHY, K; LUITEN, PGM; NYAKAS, C

    1995-01-01

    The long-term effects of prenatal and early postnatal ethanol exposure were assessed in adult (5-month), aged (24-month), and senescent (30-month) rats on non-aggressive intermale social behavior, and on black-white discrimination and spatial learning behaviors. Furthermore, the effects of chronic

  3. Regulation of activity-regulated cytoskeleton protein (Arc) mRNA after acute and chronic electroconvulsive stimulation in the rat

    DEFF Research Database (Denmark)

    Larsen, M H; Olesen, M; Woldbye, D P D

    2005-01-01

    The temporal profile of Arc gene expression after acute and chronic electroconvulsive stimulations (ECS) was studied using semi-quantitative in situ hybridisation in the rat cortex. A single ECS strongly and temporarily increased Arc mRNA levels in dentate granular cells with maximal induction seen...

  4. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads

    2003-01-01

    compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

  5. Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat.

    Science.gov (United States)

    Han, Ying; Lin, Min; Wang, Xiaobin; Guo, Keke; Wang, Shanshan; Sun, Mengfei; Wang, Jiao; Han, Xiaoyu; Fu, Ting; Hu, Yang; Fu, Jihua

    2015-03-01

    Our previous study has demonstrated that long-term stress, known as chronic stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic pathways were impacted by CS in the HFD-fed rat. Male Sprague-Dawley rats (6 weeks of age, n = 8 per group) were fed with either standard diet or HFD with or without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and lipid profile markers in serum and liver, and enzymes involved in de novo lipogenesis (DNL) of fatty acids (FAs) and cholesterol, β-oxidation, FAs uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly in the liver were detected. CS exposure reduced hepatic lipidosis but further elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats. There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR and western blot assays showed that CS exposure significantly promoted hepatic VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact on DNL, β-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed rats. This phenomenon was in accordance with elevated serum glucocorticoid level. The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed rats is VLDL assembly which might be regulated by glucocorticoid.

  6. Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

    Science.gov (United States)

    Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

    2014-01-01

    NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

  7. Substance P differentially modulates firing rate of solitary complex (SC neurons from control and chronic hypoxia-adapted adult rats.

    Directory of Open Access Journals (Sweden)

    Nicole L Nichols

    Full Text Available NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS. Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus neurons from control and chronic hypoxia-adapted (CHx adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.

  8. Chronic social isolation suppresses proplastic response and promotes proapoptotic signalling in prefrontal cortex of Wistar rats.

    Science.gov (United States)

    Djordjevic, Ana; Adzic, Miroslav; Djordjevic, Jelena; Radojcic, Marija B

    2010-08-15

    Successful adaptation to stress involves synergized actions of glucocorticoids and catecholamines at several levels of the CNS, including the prefrontal cortex (PFC). Inside the PFC, hormonal signals trigger concerted actions of transcriptional factors, such as glucocorticoid receptor (GR) and nuclear factor kappa B (NFkappaB), culminating in a balanced, proadaptive expression of their common genes, such as proplastic NCAM and/or apoptotic Bax and Bcl-2. In the present study, we hypothesized that chronic stress may compromise the balance between GR and NFkappaB signals and lead to an altered/maladaptive expression of their cognate genes in the PFC. Our results obtained with Wistar rats exposed to chronic social isolation indicated alterations of the GR relative to the NFkappaB, in favor of the GR, in both the cytoplasmic and the nuclear compartments of the PFC. Although these alterations did not affect the induction of proplastic NCAM gene, they decreased the NCAM sialylation necessary for plastic response and caused marked relocation of the mitochondrial membrane antiapoptotic Bcl-2 protein to its cytoplasmic form. Moreover, the compromised PSA-NCAM plastic response found under chronic stress was sustained after exposure of animals to the subsequent acute stress, whereas the proapoptotic signals were further emphasized. It is concluded that chronic social isolation of Wistar animals leads to a maladaptive response of the PFC, considering the diminishment of its plastic potential and potentiating of apoptosis. Such conditions in the PFC are likely to compromise its ability to interact with other CNS structures, such as the hippocampus, which is necessary for successful adaptation to stress. (c) 2010 Wiley-Liss, Inc.

  9. Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

    Science.gov (United States)

    Rezin, Gislaine T; Scaini, Giselli; Ferreira, Gabriela K; Cardoso, Mariane R; Gonçalves, Cinara L; Constantino, Larissa S; Deroza, Pedro F; Ghedim, Fernando V; Valvassori, Samira S; Resende, Wilson R; Quevedo, João; Zugno, Alexandra I; Streck, Emilio L

    2012-12-01

    Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.

  10. Effects of chronic stress on the brain – the evidence from morphological examinations of hippocampus in a chronic unpredictable stress (CUS model in rats

    Directory of Open Access Journals (Sweden)

    Joanna Sekita-Krzak

    2016-12-01

        Abstract Background. Chronic stress exposure deteriorates memory and increases the risk of psychiatric disorders, including depression. Objectives. The objective of this study was to perform morphological studies in experimental model of neuropsychiatric disorder and to assess histologically the effect of chronic unpredictable stress procedure (CUS influence on hippocampus. Material and methods. Chronic unpredictable stress procedure (CUS was applied for 8 weeks in rats by the modified method described by Katz et al. Experimental model of neuropsychiatric disorder was used based on morphological studies of hippocampal formation. Results. Stress-induced alterations were observed in the hippocampus. Nerve cell changes included  neuron shrinkage and dendritic remodeling. The most vulnerable hippocampal cells to chronic stress were CA3 and CA4 pyramidal neurons. In dentate gyrus chronic stress led to granule neuron shrinkage and slight exacerbation of apoptosis in the polygonal cell layer. CUS led to statistically significant changes in quantitative characteristics of the CA3 and CA4 neuron size and nuclei diameter. Conclusions. Chronic stress induces degeneration of hippocampal neurons. The observed neuronal changes indicate the damage of the neurons did not involve neither apoptosis nor necrosis Similarity between histological changes obtained in 8-week long CUS procedure applied in our research and morphological changes described in depressed patients confirms the usefulness of the applied stress procedure as the experimental model of depression.   Key words: stress, depression, hippocampus, chronic unpredictable stress procedure (CUS, animal model, morphology.

  11. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

    Science.gov (United States)

    Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

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

    Science.gov (United States)

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

    1991-11-01

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

  13. [Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].

    Science.gov (United States)

    Liu, Xu-hua; Chen, Yu; Wang, Tai-ling; Lu, Jun; Zhang, Li-jie; Song, Chen-zhao; Zhang, Jing; Duan, Zhong-ping

    2007-10-01

    To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment. Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure. We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

  14. Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

    Science.gov (United States)

    Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

    2010-08-01

    Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

  15. Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats.

    Science.gov (United States)

    Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

    2009-12-01

    The combined effects of high fat diet (HFD) and chronic stress on the hippocampus-dependent spatial learning and memory were studied in rats using the radial arm water maze (RAWM). Chronic psychosocial stress and/or HFD were simultaneously administered for 3 months to young adult male Wister rats. In the RAWM, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied on a daily basis until the animal reaches days to criterion (DTC) in the 12th learning trial and in memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC. Chronic stress, HFD and chronic stress/HFD animal groups showed impaired learning as indicated by committing significantly (Pchronic stress, HFD and chronic stress/HFD groups showed significantly impaired performance compared to control group. Additionally, the stress/HFD was the only group that showed significantly impaired performance in memory tests on the 5th training day, suggesting more severe memory impairment in that group. Furthermore, DTC value for above groups indicated that chronic stress or HFD, alone, resulted in a mild impairment of spatial memory, but the combination of chronic stress and HFD resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and HFD produced more deleterious effects on hippocampal cognitive function than either chronic stress or HFD alone.

  16. The organ specificity in pathological damage of chronic intermittent hypoxia: an experimental study on rat with high-fat diet.

    Science.gov (United States)

    Wang, Hui; Tian, Jian-li; Feng, Shu-zhi; Sun, Ning; Chen, Bao-yuan; Zhang, Yun

    2013-09-01

    It is known today that sleep apnea hypopnea syndrome and its characteristic chronic intermittent hypoxia can cause damages to multiple organs, including the cardiovascular system, urinary system, and liver. It is still unclear, however, whether the damage caused by sleep apnea hypopnea syndrome and the severity of the damage are organ-specific. This research observed the pathological effects of chronic intermittent hypoxia on rat's thoracic aorta, myocardium, liver, and kidney, under the condition of lipid metabolism disturbance, through establishing the rat model of chronic intermittent hypoxia with high-fat diet by imitating the features of human sleep apnea hypopnea syndrome. In this model, 24 male Wistar rats were randomly divided into three groups: a control group fed by regular diet, a high-fat group fed by high-fat diet, and a high-fat plus intermittent hypoxia group fed by high-fat diet and treated with intermittent hypoxia 7 h a day. At the end of the ninth week, the pathological changes of rat's organs, including the thoracic aorta, myocardium, liver, and kidney are observed (under both optical microscopy and transmission electron microscopy). As the result of the experiment shows, while there was no abnormal effect observed on any organs of the control group, slight pathological changes were found in the organs of the high-fat group. For the high-fat plus intermittent hypoxia group, however, remarkably severer damages were found on all the organs. It also showed that the severity of the damage varies by organ in the high-fat plus intermittent hypoxia group, with the thoracic aorta being the worst, followed by the liver and myocardium, and the kidney being the slightest. Chronic intermittent hypoxia can lead to multiple-organ damage to rat with high-fat diet. Different organs appear to have different sensitivity to chronic intermittent hypoxia.

  17. Relief of chronic partial ureteral obstruction attenuates salt-sensitive hypertension in rats

    DEFF Research Database (Denmark)

    Carlström, M.; Wåhlin, N.; Skøtt, Ole

    2007-01-01

    shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. METHODS: Partial unilateral ureteral...... obstruction was created in 3-week-old male Sprague-Dawley rats and blood pressure was measured telemetrically 4-6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral...... nephrectomy. RESULTS: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 +/- 15 microGU mL(-1) vs. 96 +/- 12 microGU mL(-1), respectively...

  18. Lead elimination by ICRF 158 in rats after chronic lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Witting, U; Hultsch, E

    1981-02-01

    Lead elimination by ICRF 158, a lipophilic derivative of ethylene-diaminetetra-acetate (EDTA), was investigated in rats after chronic lead exposure. The animals had received a lead concentration of 550 ppm in their drinking water for 140 days. Subsequent treatment with ICRF 158 for 30 days led to increased mobilization and elimination of incorporated lead, and the lead-induced inhibition of hemosynthesis was removed. ICR 158 produced no renal damage in excess to lead-induced tubular nephrosis. Separate toxicity tests in mice demonstrated that is less toxic than CaNa/sub 2/EDTA. ICRF 158 does not form stable complexes with lead ions in vitro. The mechanism of action of this lipophilic EDTA derivative is compared to that of its hydrophilic correspondent, the chelating agent CaNa/sub 2/EDTA.

  19. Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

    Directory of Open Access Journals (Sweden)

    Zhiyong Wang

    2017-01-01

    Full Text Available Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP, a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI. The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

  20. [Teratologic cranio-encephalic effects of chronic thinner inhalation in progenitors, in rats and humans].

    Science.gov (United States)

    Barroso-Moguel, R; Villeda-Hernández, J; Méndez-Armenta, M

    1991-01-01

    Inhalation of thinner by youngsters and adolescents is an increasing drug abuse problem in Mexico. It presents serious repercussions upon socio-economic, cultural, legal and health (neurologic and psychiatric) problems. We report a comparative study in humans and rats which demonstrate the embryotoxic and craneo encephalic teratologic effects in the children and brood of progenitors who have chronically inhaled thinner (in the case of pregnant women, before, at the beginning and throughout pregnancy). Inhaled thinner passes directly to the blood stream and crosses the placentary barrier freely reaching the embryo. It may cause craneal bone and partial or total encephalon agenesia, added to macro and microscopic lesions secondary to direct aggression to the neuroepithelial germ cells. Abortions and premature labor with weight and size underdeveloped products and placentary hemorrhages occur. Usually these die, but if they survive they show trascendental mental retardation, as well as neurologic and psychiatric sequels.

  1. Intestinal inflammation in TNBS sensitized rats as a model of chronic inflammatory bowel disease

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    N. Selve

    1992-01-01

    Full Text Available An enteritis, based on a delayed-type hypersensitivity reaction, was induced in TNBS (2,4,4-trinitrobenzenesulphonic acid sensitized rats by multiple intrajejunal challenge with TNBS via an implanted catheter. This treatment induced chronic inflammation of the distal small intestine characterized by intense hyperaemia, oedema and gut wall thickening as assessed by macroscopic scoring and weighing a defined part of the dissected intestine. Histologically, the inflammatory response included mucosal and submucosal cell infiltration by lymphocytes and histiocytes, transmural granulomatous inflammation with multinucleated cells and activated mesenteric lymph nodes. Ex vivo stimulated release of the inflammatory mediator LTB4 in the dissected part of the intestine was increased following TNBS treatment. Drug treatment with sulphasalazine or 5-aminosalicylic acid improved the enteritis score and attenuated TNBS induced oedema formation and LTB4 production. The applicability and relevance of this new model are discussed with respect to drug development and basic research of inflammatory bowel diseases.

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

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    Khedr LH

    2015-11-01

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

  3. Comparative antistress effect of Vitis vinifera and Withania somnifera using unpredictable chronic mild stress model in rats

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    Manish Pal Singh

    2016-07-01

    Full Text Available Introduction: The human society has become complex. However, our physiological responses designed to cope with the ever-increasing adverse situations have not evolved appreciably during the past thousand years. The failure of successful adaptation during stressful situations has resulted in stress-related illnesses. Methods: The objective of the present study was to carry out a comparative assessment of anti-stress effect of Vitis vinifera and Withania somnifera using unpredictable chronic mild stress model in rats. Long-term exposure to multiple stressors can cause depression. The unpredictable chronic administration of various mild stresses, a procedure known as “unpredictable chronic mild stress”, is one of the best-validated rodent models to study stress in animals, for its good etiological and predictive validity. Result: Diazepam, Withania somnifera, Vitis vinifera administration dose dependently reversed the increase in immobility period in stressed rats. In the study of locomotion activity of rats in elevated plus maze apparatus, Stress treated control group rats showed less no of entries in open arm and also less time spent in open arm. Vitis vinifera treated (p<0.0001, Withania somnifera treated (p<0.0001 and Diazepam treated group showed (p<0.0001 no. of entries in open arms which were more than control group and stressed groups. Stressed group produce less average time spent in open arm as compared to treatment groups as Withania somnifera (p<0.05, Vitis vinifera and diazepam. Withania somnifera group showed significant antistress locomotry behaviour in rats. Administration of Vitis vinifera, Withania somnifera and diazepam during stress period restored the ambulatory behaviour of the rats which can be correlated with restoration of plasma corticosterone level. Finally, the results of the present study justified that Withania somnifera, Vitis vinifera and diazepam exhibited significant antistress activity in rats.

  4. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

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    Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

    2016-01-01

    Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

  5. Alterations of apparent diffusion coefficient (ADC) in the brain of rats chronically exposed to lead acetate.

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    López-Larrubia, Pilar; Cauli, Omar

    2011-03-15

    Diffusion-weighted imaging (DWI) allows the assessment of the water apparent diffusion coefficient (ADC), a measure of tissue water diffusivity which is altered during different pathological conditions such as cerebral oedema. By means of DWI, we repeatedly measured in the same rats apparent diffusion coefficient ADC in different brain areas (motor cortex (MCx), somato-sensory cortex (SCx), caudate-putamen (CPu), hippocampus (Hip), mesencephalic reticular formation (RF), corpus callosum (CC) and cerebellum (Cb)) after 1 week, 4 and 12 weeks of lead acetate exposure via drinking water (50 or 500 ppm). After 12 weeks of lead exposure rats received albumin-Evans blue complex administration and were sacrificed 1h later. Blood-brain barrier permeability and water tissue content were determined in order to evaluate their relationship with ADC changes. Chronic exposure to lead acetate (500 ppm) for 4 weeks increased ADC values in Hip, RF and Cb but no in other brain areas. After 12 weeks of lead acetate exposure at 500 ppm ADC is significantly increased also in CPu and CC. Brain areas displaying high ADC values after lead exposure showed also an increased water content and increased BBB permeability to Evans blue-albumin complex. Exposure to 50 ppm for 12 weeks increased ADC values and BBB permeability in the RF and Cb. In summary, chronic lead exposure induces cerebral oedema in the adult brain depending on the brain area and the dose of exposure. RF and Cb appeared the most sensitive brain areas whereas cerebral cortex appears resistant to lead-induced cerebral oedema. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

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    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  7. Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction.

    Science.gov (United States)

    Liu, XinHua; Pan, LiLong; Gong, QiHai; Zhu, YiZhun

    2010-12-15

    Leonurine, an alkaloid typically found in Herba leonuri, is known to have both antioxidant and cardioprotective properties. In the present study, we investigated the cardioprotective mechanism of leonurine the in vivo rat model of chronic myocardial ischemia and in vitro H9c2 cardiac myocyte model of oxidative stress. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Rats were divided into sham, myocardial ischemia+saline, and myocardial ischemia+leonurine (15 mg/kg/day). Cardiac function was recorded by catheterization. Apoptosis-related factor vascular endothelial growth factor (VEGF), survivin, Bcl-2 and Bax and pro-survival signaling pathways Akt, hypoxia inducible factor (HIF)-1α were measured by Western blotting or RT-PCR. Our results showed leonurine significantly improved myocardial function as evidenced by the decreased left ventricle end-diastolic pressure and the increased +dP/dt. Interestingly, leonurine increased the phosphorylation of Akt, the protein and gene expression of Bcl-2, but it reduced the protein and gene expression of Bax in vivo. Meanwhile leonurine significantly increased Akt phosphorylation in a concentration-dependent manner in H9c2 cardiac myocyte induced by oxidative stress in vitro, which was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. Furthermore, leonurine not only increased the expression of HIF-1α but also the expression of survivin and VEGF. The results of present study demonstrated, for the first time that leonurine has potent anti-apoptotic effects after chronic myocardial ischemia mediated by activating the PI3K/Akt signaling pathway. Angiogenic mechanisms may be partially responsible for such an effect, which needs to be studied further. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Beneficial Effect of Moderate Exercise in Kidney of Rat after Chronic Consumption of Cola Drinks.

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    Gabriel Cao

    Full Text Available The purpose of this study was to investigate the effect of moderate intensity exercise on kidney in an animal model of high consumption of cola soft drinks.Forty-eight Wistar Kyoto rats (age: 16 weeks; weight: 350-400 g were assigned to the following groups: WR (water runners drank water and submitted to aerobic exercise; CR (cola runners drank cola and submitted to aerobic exercise; WS (water sedentary and CS (cola sedentary, not exercised groups. The aerobic exercise was performed for 5 days per week throughout the study (24 weeks and the exercise intensity was gradually increased during the first 8 weeks until it reached 20 meters / minute for 30 minutes. Body weight, lipid profile, glycemia, plasma creatinine levels, atherogenic index of plasma (AIP and systolic blood pressure (SBP were determined. After 6 months all rats were sacrificed. A kidney histopathological score was obtained using a semiquantitative scale. Glomerular size and glomerulosclerosis were estimated by point-counting. The oxidative stress and pro-inflammatory status were explored by immunohistochemistry. A one way analysis of variance (ANOVA with Tukey-Kramer post-hoc test or the Kruskal-Wallis test with Dunn's post-hoc test was used for statistics. A value of p < 0.05 was considered significant.At 6 months, an increased consumption of cola soft drink was shown in CS and CR compared with water consumers (p<0.0001. Chronic cola consumption was associated with increased plasma triglycerides, AIP, heart rate, histopathological score, glomerulosclerosis, oxidative stress and pro-inflammatory status. On the other hand, moderate exercise prevented these findings. No difference was observed in the body weight, SBP, glycemia, cholesterol and plasma creatinine levels across experimental groups.This study warns about the consequences of chronic consumption of cola drinks on lipid metabolism, especially regarding renal health. Additionally, these findings emphasize the protective

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

    Science.gov (United States)

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

    2015-11-01

    Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats.

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    Gu, Qi; Wang, Bing; Zhang, Xiao-Feng; Ma, Yan-Ping; Liu, Jian-Dong; Wang, Xiao-Ze

    2014-08-01

    Aging leads to large vessel arterial stiffening and endothelial dysfunction, which are important determinants of cardiovascular risk. The aim of present work was to assess the effects of chronic aerobic exercise training on aortic stiffening and endothelial dysfunction in aged rats and investigate the underlying mechanism about mitochondrial function. Chronic aerobic exercise training attenuated aortic stiffening with age marked by reduced collagen concentration, increased elastin concentration and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by improved endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Chronic aerobic exercise training abated oxidative stress and nitrosative stress in aortas of aged rats. More importantly, we found that chronic aerobic exercise training in old rats preserved aortic mitochondrial function marked by reduced reactive oxygen species (ROS) formation and mitochondrial swelling, increased ATP formation and mitochondrial DNA content, and restored activities of complexes I and III and electron-coupling capacity between complexes I and III and between complexes II and III. In addition, it was found that chronic aerobic exercise training in old rats enhanced protein expression of uncoupling protein 2 (UCP-2), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), manganese superoxide dismutase (Mn-SOD), aldehyde dehydrogenase 2 (ALDH-2), prohibitin (PHB) and AMP-activated kinase (AMPK) phosphorylation in aortas. In conclusion, chronic aerobic exercise training preserved mitochondrial function in aortas, which, at least in part, explained the aorta-protecting effects of exercise training in aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid

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    Markus K. Larsson

    2015-01-01

    Full Text Available Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6, olanzapine (2 mg/kg, n = 6, and clozapine (20 mg/kg, n = 6 or saline ( n = 6 for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.

  12. Effect of chronic ethanol ingestion and exercise training on skeletal muscle in rat.

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    Vila, L; Ferrando, A; Voces, J; Cabral de Oliveira, C; Prieto, J G; Alvarez, A I

    2001-09-01

    The aim of this study was to investigate the interactive effects of exercise training and chronic ethanol consumption on metabolism, capillarity, and myofibrillar composition in rat limb muscles. Male Wistar rats were treated in separate groups as follows: non exercised-control; ethanol (15%) in animals' drinking water for 12 weeks; exercise training in treadmill and ethanol administration plus exercise for 12 weeks. Ethanol administration decreased capillarity and increased piruvate kinase and lactate dehydrogenase activities in white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase activity and decreased cross-sectional area of type I, IIa, and IIb fibres. Exercise increased capillarity in all four limb muscles and decreased type I fibre area in plantaris. The decreased capillarity effect induced by ethanol in some muscles, was ameliorated when alcohol was combined with exercise. While alcoholic myopathy affects predominantly type IIb fibres, ethanol administration and aerobic exercise in some cases can affect type I and type IIa fibre areas. The exercise can decrease some harmful effects produced by ethanol in the muscle, including the decrease in the fibre area and capillary density.

  13. The Effect of Chronic Methamphetamine Exposure on the Hippocampal and Olfactory Bulb Neuroproteomes of Rats.

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    Rui Zhu

    Full Text Available Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH is one of the most abused drugs and is known to cause brain damage after repeated exposure. In this paper, we conducted a neuroproteomic study to evaluate METH-induced brain protein dynamics, following a two-week chronic regimen of an escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantification was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in the hippocampus and 7 in the olfactory bulb underwent a significant alteration as a result of exposing rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis.

  14. Differential effects of chronic fluoxetine on the behavior of dominant and subordinate naked mole-rats.

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    Mongillo, Daniel L; Kosyachkova, Ekaterina A; Nguyen, Tam M; Holmes, Melissa M

    2014-01-01

    Naked mole-rats are eusocial rodents that live in large subterranean colonies with a strict reproductive and social hierarchy. The breeding female (referred to as the queen) and 1 to 3 breeding males are the only reproductive members of the colony. Breeders are socially dominant and all other colony members are non-reproductive subordinates. The effects of manipulating the serotonergic neurotransmitter system on aggression and dominance behaviors are well studied in many species, but not in eusocial rodents like the naked mole-rat. The current study investigated how the serotonergic system influences aggressive/dominant behaviors in this species. To do this, two separate but related experiments were conducted: the effects of fluoxetine hydrochloride (FLX) on status-specific behaviors of subordinates (Experiment 1) and dominant queens (Experiment 2) were evaluated both in-colony and in a social-pairing paradigm. In accordance with our main hypothesis, chronic treatment of FLX attenuated the frequency and duration of aggression in queens, but not subordinates, when paired with an unfamiliar conspecific. Further exploration of pharmacological manipulation on status-specific behaviors of this eusocial species may elucidate the neurobiological mechanisms underlying their unique and rigid social hierarchy. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Effect of chronic morphine treatment on β-endorphin biosynthesis by the rat neurointermediate lobe

    International Nuclear Information System (INIS)

    Gianoulakis, C.; Drouin, J.-N.; Seidah, N.G.; Kalant, H.; Chretien, M.

    1981-01-01

    The effect of chronic morphine treatment on the in vitro biosynthesis of β-endorphin by rat pars intermedia was investigated. Tolerance and physical dependence were induced in 200 g rats by the subcutaneous implantation of 75 mg morphine pellets for either 3 days or 15 days. Immediately following sacrifice of the animals the neurointermediate lobes were removed and incubated with [ 3 H]phenylalanine. The protein extracts of the lobes were analyzed for the incorporation of the labelled amino acid into total protein, pro-opiomelanocortin, β-lipotropin (β-LPH) and β-endorphin. The biosynthesized products were purified by immunoprecipitation with an antiserum to β-endorphin. The identity and purity of β-endorphin were verified by polyacrylamide disc gel electrophoresis with sodium dodecyl sulfate, and mircrosequencing. The identity of pro-opiomelanocortin (POMC) was verified by peptide mapping of its tryptic digestion products. The results showed that morphine treatment induced a decrease in the incorporation of the radioactive amino acid into total protein, pro-opiomelanocortin, β-LPH and β-endorphin. The decrease was more pronounced for the incorporation into β-LPH and β-endorphin than into pro-opiomelanocortin and total proteins, suggesting an effect of morphine treatment on the processing of the pro-opiomelanocortin to its final maturation products. (Auth.)

  16. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    Science.gov (United States)

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion.

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    Levy, E; Hasin, Y; Navon, G; Horowitz, M

    1997-05-01

    Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of rats subjected to a combined chronic stress of heat acclimation and swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC), DP, and SP were measured during progressive graded ischemia, total ischemia (TI), and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy. During normoperfusion, SP and cardiac efficiency (derived from rate-pressure product-oxygen consumption relationships) were the highest in the 2-mo EXAC hearts (P pool and there was a delayed decline in intracellular pH. On reperfusion, these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo EXAC heart demonstrating significantly faster high-energy phosphate salvage, improved diastolic function, and pulse pressure recovery. The data attest to the beneficial effects of heat acclimation on cardiac mechanics of trained rats during normoperfusion and cardiac protection on ischemia and reperfusion. Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia and improved energy salvage on reperfusion contribute synergistically to this potent beneficial effect.

  18. Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats.

    Science.gov (United States)

    Tian, Jie; Gu, Yiwen; Su, Diansan; Wu, Yichao; Wang, Xiangrui

    2009-02-01

    The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.

  19. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

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    Ibrahim M Salman

    2015-08-01

    Full Text Available Chronic kidney disease (CKD is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n=16 were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2 and central chemoreflex (hypercapnia: 7% CO2 activation and acute stress (open-field exposure, were measured. As indicators of renal function, urinary protein (UPro and creatinine (Ucr levels were assessed. LPK rats had higher resting RSNA (1.2±0.1 vs. 0.6±0.1 µV, p<0.05 and MAP (151±8 vs. 97±2 mmHg, p<0.05 compared to Lewis. MAP was negatively correlated with Ucr (r=-0.80, p=0.002 and positively correlated with RSNA (r=0.66, p=0.014, with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p<0.05. This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

  20. Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

    International Nuclear Information System (INIS)

    Pereira, F.A.; Mattar, R.; Facincani, I.; Defino, H.L.A.; Ramalho, L.N.Z.; Jorgetti, V.; Volpon, J.B.; Paula, F.J.A. de

    2012-01-01

    Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility

  1. Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, F.A. [Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattar, R. [1Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Facincani, I. [Departamento de Pediatria e Neonatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Defino, H.L.A. [Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Ramalho, L.N.Z. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Jorgetti, V. [Departamento de Nefrologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Volpon, J.B. [Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Paula, F.J.A. de [Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-09-14

    Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

  2. Attenuated fatigue in slow twitch skeletal muscle during isotonic exercise in rats with chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Morten Munkvik

    Full Text Available During isometric contractions, slow twitch soleus muscles (SOL from rats with chronic heart failure (chf are more fatigable than those of sham animals. However, a muscle normally shortens during activity and fatigue development is highly task dependent. Therefore, we examined the development of skeletal muscle fatigue during shortening (isotonic contractions in chf and sham-operated rats. Six weeks following coronary artery ligation, infarcted animals were classified as failing (chf if left ventricle end diastolic pressure was >15 mmHg. During isoflurane anaesthesia, SOL with intact blood supply was stimulated (1s on 1s off at 30 Hz for 15 min and allowed to shorten isotonically against a constant afterload. Muscle temperature was maintained at 37°C. In resting muscle, maximum isometric force (F(max and the concentrations of ATP and CrP were not different in the two groups. During stimulation, F(max and the concentrations declined in parallel sham and chf. Fatigue, which was evident as reduced shortening during stimulation, was also not different in the two groups. The isometric force decline was fitted to a bi-exponential decay equation. Both time constants increased transiently and returned to initial values after approximately 200 s of the fatigue protocol. This resulted in a transient rise in baseline tension between stimulations, although this effect which was less prominent in chf than sham. Myosin light chain 2s phosphorylation declined in both groups after 100 s of isotonic contractions, and remained at this level throughout 15 min of stimulation. In spite of higher energy demand during isotonic than isometric contractions, both shortening capacity and rate of isometric force decline were as well or better preserved in fatigued SOL from chf rats than in sham. This observation is in striking contrast to previous reports which have employed isometric contractions to induce fatigue.

  3. Chronic impairments in spatial learning and memory in rats previously exposed to chlorpyrfos or diisopropylfluorophosphate.

    Science.gov (United States)

    Terry, A V; Beck, W D; Warner, S; Vandenhuerk, L; Callahan, P M

    2012-01-01

    The acute toxicity of organophosphates (OPs) has been studied extensively; however, much less attention has been given to the subject of repeated exposures that are not associated with overt signs of toxicity (i.e., subthreshold exposures). The objective of this study was to determine if the protracted spatial learning impairments we have observed previously after repeated subthreshold exposures to the insecticide chlorpyrifos (CPF) or the alkylphosphate OP, diisopropylfluorophosphate (DFP) persisted for longer periods after exposure. Male Wistar rats (beginning at two months of age) were initially injected subcutaneously with CPF (10.0 or 18.0mg/kg) or DFP (0.25 or 0.75 mg/kg) every other day for 30 days. After an extended OP-free washout period (behavioral testing begun 50 days after the last OP exposure), rats previously exposed to CPF, but not DFP, were impaired in a radial arm maze (RAM) win-shift task as well as a delayed non-match to position procedure. Later experiments (i.e., beginning 140 days after the last OP exposure) revealed impairments in the acquisition of a water maze hidden platform task associated with both OPs. However, only rats previously exposed to DFP were impaired in a second phase of testing when the platform location was changed (indicative of deficits of cognitive flexibility). These results indicate, therefore, that repeated, subthreshold exposures to CPF and DFP may lead to chronic deficits in spatial learning and memory (i.e., long after cholinesterase inhibition has abated) and that insecticide and alkylphosphate-based OPs may have differential effects depending on the cognitive domain evaluated. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Short- and long-term antidepressant effects of ketamine in a rat chronic unpredictable stress model.

    Science.gov (United States)

    Jiang, Yinghong; Wang, Yiqiang; Sun, Xiaoran; Lian, Bo; Sun, Hongwei; Wang, Gang; Du, Zhongde; Li, Qi; Sun, Lin

    2017-08-01

    This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short-term) or 7 weeks after ketamine treatment (long-term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety-like behavior (OF and EPM), forced swimming (FS), and water maze (WM). Results: Short-term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety-eliciting situations. No significant differences in these behaviors were obtained under conditions of long-term ketamine administration ( p  > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long-term effects of ketamine (* p   .05). Taken together these findings demonstrate that a short-term administration of ketamine induced rapid antidepressant-like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long-term treatment regime.

  5. Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

    Science.gov (United States)

    Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

    2015-12-01

    Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  6. High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure

    DEFF Research Database (Denmark)

    Saeed, Aso; DiBona, Gerald F; Grimberg, Elisabeth

    2014-01-01

    This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without...... arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous...... adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic...

  7. [Expressions of neuropathic pain-related proteins in the spinal cord dorsal horn in rats with bilateral chronic constriction injury].

    Science.gov (United States)

    Shen, Le; Li, Xu; Wang, Hai-tang; Yu, Xue-rong; Huang, Yu-guang

    2013-12-01

    To evaluate the pain-related behavioral changes in rats with bilateral chronic constriction injury(bCCI)and identify the expressions of neuropathic pain-related proteins. The bCCI models were established by ligating the sciatic nerves in female Sprague Dawley rats. Both mechanical hyperalgesia and cold hyperalgesia were evaluated through electronic von Frey and acetone method. Liquid chromatography-mass spectrometry/mass spectrometry was applied to characterize the differentially expressed proteins. Both mechanical withdrawal threshold and cold hyperalgesia threshold decreased significantly on the postoperative day 7 and 14, when compared with na ve or sham rats(P <0.05). Twenty five differentially expressed proteins associated with bilateral CCI were discovered, with eighteen of them were upregulated and seven of them downregulated. The bCCT rats have remarkably decreased mechanical and cold hyperalgesia thresholds. Twenty five neuropathic pain-related proteins are found in the spinal cord dorsal horn.

  8. The potential anti-inflammatory effect of tetrahydrobiopterin administration in renal mass reduction-induced chronic renal failure in rats

    International Nuclear Information System (INIS)

    Korish, Aida A.; Arafah, Maha M.

    2007-01-01

    Objective was to investigate the impact of tetrahydrobiopterin (BH4) supplementation on the markers of inflammation and on the histological picture of the kidney in chronic renal failure C-reactive protein (CRF) induced in rats by subtotal nephrectomy (SNx). This study was performed at the Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia during the period from December 2005 to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister rats and another 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received 10 mg/kg-1 BH4 intraperitoneally daily for 4 weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde (MDA) and kidney functions were measured in all rats. Histopathological examination of kidney tissues was also performed. Untreated CRF rats showed significant elevation of plasma CRP, IL-6 and MDA levels and significant decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis and interstitial tubular infiltration with inflammatory cells in comparison with the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, MDA levels and decreased tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats. Supplementation with exogenous BH4 decreased markers of inflammation and protected the kidney against post-renal mass reduction histological damage. Restoration of intracellular BH4 balance could normalize nitrous oxide production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality of this disease. (author)

  9. Effects of chronic mild stress on the development of drug dependence in rats.

    Science.gov (United States)

    Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Litwa, Ewa; Willner, Paul

    2014-09-01

    There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

  10. Protective effect of fenspiride on the bronchi in rats with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Kuzubova, N A; Lebedeva, E S; Fedin, A N; Dvorakovskaya, I V; Titova, O N

    2013-06-01

    We studied the effect of a non-steroidal anti-inflammatory drug fenspiride on contractive activity of bronchial smooth muscles on the model of chronic obstructive pulmonary disease of rats induced by 60-day exposure to nitrogen dioxide. The administration of fenspiride during the acute stage of the disease (day 15) abolished the constricting effect of the pollutant on the bronchial smooth muscles. Dilatation effect of fenspiride in a low dose (0.15 mg/kg) was mediated by its interaction with nerve endings of bronchial capsaicin-sensitive nerve C-fibers. The interaction of drug with receptors of C-fibers prevented neurogenic inflammation, which was confirmed by the absence of structural changes in the lungs typical of this pathology. The broncholytic effect of fenspiride in a high dose (15 mg/kg) was mediated by not only afferent pathways, but also its direct relaxing action on smooth muscle cells. The observed anti-inflammatory and bronchodilatation effect of fenspiride in very low doses can be used for prevention of chronic obstructive pulmonary disease in risk-group patients contacting with aggressive environmental factors.

  11. Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats

    Directory of Open Access Journals (Sweden)

    A. R. Navarro-Cruz

    2017-01-01

    Full Text Available The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions.

  12. Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model.

    Science.gov (United States)

    Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho; Bless, Diane M

    2016-03-01

    Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring.

  13. Protective effects of triptolide on retinal ganglion cells in a rat model of chronic glaucoma

    Directory of Open Access Journals (Sweden)

    Yang F

    2015-11-01

    Full Text Available Fan Yang, Dongmei Wang, Lingling Wu, Ying Li Ophthalmology Department, Peking University Third Hospital, Beijing, People’s Republic of China Purpose: To study the effects of triptolide, a Chinese herb extract, on retinal ganglion cells (RGCs in a rat model of chronic glaucoma.Methods: Eighty Wistar rats were randomly divided into triptolide group (n=40 and normal saline (NS group (n=40. Angle photocoagulation was used to establish the model of glaucoma, with right eye as laser treated eye and left eye as control eye. Triptolide group received triptolide intraperitoneally daily, while NS group received NS. Intraocular pressure (IOP, anti-CD11b immunofluorescent stain in retina and optic nerve, RGCs count with Nissel stain and microglia count with anti-CD11b immunofluorescence stain in retina flat mounts, retinal tumor necrosis factor (TNF-α mRNA detection by reverse transcription–polymerase chain reaction, and double immunofluorescent labeling with anti-TNF-α and anti-CD11b in retinal frozen section were performed.Results: Mean IOP of the laser treated eyes significantly increased 3 weeks after photocoagulation (P<0.05, with no statistical difference between the two groups (P>0.05. RGCs survival in the laser treated eyes was significantly improved in the triptolide group than the NS group (P<0.05. Microglia count in superficial retina of the laser treated eyes was significantly less in the triptolide group (30.40±4.90 than the NS group (35.06±7.59 (P<0.05. TNF-α mRNA expression in the retina of the laser treated eyes in the triptolide group decreased by 60% compared with that in the NS group (P<0.01. The double immunofluorescent labeling showed that TNF-α was mainly distributed around the microglia.Conclusion: Triptolide improved RGCs survival in this rat model of chronic glaucoma, which did not depend on IOP decrease but might be exerted by inhibiting microglia activities and reducing TNF-α secretion. Keywords: glaucoma, triptolide

  14. Tolerance to disulfiram induced by chronic alcohol intake in the rat.

    Science.gov (United States)

    Tampier, Lutske; Quintanilla, María Elena; Israel, Yedy

    2008-06-01

    Disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism, is an effective medication when its intake is supervised by a third person. However, its therapeutic efficacy varies widely, in part due to the fact that disulfiram is a pro-drug that requires its transformation into an active form and because it shows a wide range of secondary effects which often prevent the use of doses that ensure full therapeutic effectiveness. In this preclinical study in rats we report the development of tolerance to disulfiram induced by the chronic ingestion of ethanol, an additional source of variation for the actions of disulfiram with possible therapeutic significance, We also addresses the likely mechanism of this effect. Wistar-derived rats bred for generations as high ethanol drinkers (UChB) were trained for either 3 days (Group A) or 30 days (Group B) to choose between ethanol (10% v/v) or water, which were freely available from 2 bottles on a 24-hour basis. Subsequently, animals in both groups were administered disulfiram or cyanamide (another inhibitor of aldehyde dehydrogenase) and ethanol intake in this free choice paradigm was determined. Animals were also administered a standard dose of 1 g ethanol/kg (i.p) and arterial blood acetaldehyde was measured. Disulfiram (12.5 and 25 mg/kg) and cyanamide (10 mg/kg) markedly inhibited ethanol intake (up to 60 to 70%) in animals that had ethanol access for only 3 days (Group A). However both drugs were inactive in inhibiting ethanol intake in animals that had consumed ethanol for 30 days (Group B). Following the injection of 1 g ethanol/kg, arterial blood acetaldehyde levels reached levels of 150 and 300 microM for disulfiram and cyanamide respectively, values which were virtually identical regardless of the length of prior ethanol intake of the animals. Chronic ethanol intake in high-drinker rats leads to marked tolerance to the aversive effects of disulfiram and cyanamide on ethanol intake despite

  15. Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization

    DEFF Research Database (Denmark)

    Lange, K H; Hougen, H P; Høiby, N

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after...... with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p = 0...... but not to prevent the chronic P. aeruginosa lung infection and inflammation caused by alginate-embedded bacteria....

  16. History of chronic stress modifies acute stress-evoked fear memory and acoustic startle in male rats.

    Science.gov (United States)

    Schmeltzer, Sarah N; Vollmer, Lauren L; Rush, Jennifer E; Weinert, Mychal; Dolgas, Charles M; Sah, Renu

    2015-01-01

    Chronicity of trauma exposure plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD). Thus, exposure to multiple traumas on a chronic scale leads to worse outcomes than acute events. The rationale for the current study was to investigate the effects of a single adverse event versus the same event on a background of chronic stress. We hypothesized that a history of chronic stress would lead to worse behavioral outcomes than a single event alone. Male rats (n = 14/group) were exposed to either a single traumatic event in the form of electric foot shocks (acute shock, AS), or to footshocks on a background of chronic stress (chronic variable stress-shock, CVS-S). PTSD-relevant behaviors (fear memory and acoustic startle responses) were measured following 7 d recovery. In line with our hypothesis, CVS-S elicited significant increases in fear acquisition and conditioning versus the AS group. Unexpectedly, CVS-S elicited reduced startle reactivity to an acoustic stimulus in comparison with the AS group. Significant increase in FosB/ΔFosB-like immunostaining was observed in the dentate gyrus, basolateral amygdala and medial prefrontal cortex of CVS-S rats. Assessments of neuropeptide Y (NPY), a stress-regulatory transmitter associated with chronic PTSD, revealed selective reduction in the hippocampus of CVS-S rats. Collectively, our data show that cumulative stress potentiates delayed fear memory and impacts defensive responding. Altered neuronal activation in forebrain limbic regions and reduced NPY may contribute to these phenomena. Our preclinical studies support clinical findings reporting worse PTSD outcomes stemming from cumulative traumatization in contrast to acute trauma.

  17. Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

    Directory of Open Access Journals (Sweden)

    Fernando B. R. da Silva

    2018-05-01

    Full Text Available Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF, pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

  18. Novel antidepressant candidate RO-05 modulated glucocorticoid receptors activation and FKBP5 expression in chronic mild stress model in rats.

    Science.gov (United States)

    Xing, Y; Hou, J; Meng, Q; Yang, M; Kurihara, H; Tian, J

    2015-04-02

    In this study, a novel TRI (triple reuptake inhibitors) antidepressant candidate RO-05 (4-[1-[1-(benzoyloxy)cyclohexyl]-2-(dimethylamino)ethyl]-phenyl benzoate) was investigated in TST (tail suspension test), FST (forced swimming test) and CMS (chronic mild stress) model. Results showed RO-05 significantly decreased the immobility time in FST and TST at 4.5-, 9-, 18-mg/kg in rats and 9-, 18-, 36-mg/kg in mice. Chronic administration of 18-mg/kg RO-05 improved the behavioral index, anhedonia and normalized the hyperactivity of HPA (hypothalamic-pituitary-adrenal axis) of CMS rats. We further investigated the possible mechanisms of RO-05 in the CMS model. Eighteen milligrams per kilogram of RO-05 chronic administration significantly reversed the increase of mRNA and protein expression of FKBP5 in the CMS rat hippocampus, which facilitated the activation of GR- (glucocorticoid receptor) and GR-responsive gene Foxo1 expression. RO-05 also elevated the expression of BDNF (brain-derived neurotrophic factor) in CMS rat hippocampus. In summary, our results indicated that RO-05 is a promising antidepressant candidate. The possible antidepressant mechanisms of RO-05 were the modulation of FKBP5 expression, GR activation, corresponding inhibition of HPA axis hyperactivity, and the increase of BDNF expression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. The influence of interferon alpha on the rat liver injured by chronic administration of carbon tetrachloride.

    Science.gov (United States)

    Madro, Agnieszka; Słomka, Maria; Celiński, Krzysztof; Chibowski, Daniel; Czechowska, Grazyna; Kleinrok, Zdzisław; Karpińska, Agnieszka

    2002-01-01

    Due to their complex and not fully known etiopathogenesis as well as difficulties in treatment, chronic hepatitis and cirrhosis still remain one of the main problems of hepatologists. Nowadays, the use of IFN alpha is considered the most effective method of treatment in chronic hepatitis. Recently, a new property of IFN, i.e. its effects on the reduction of fibrosis, has been discovered. The aim of the paper was to examine the effects of IFN alpha on biochemical parameters (AlAt and AspAt activities), on the metabolic function of the liver and its morphologic picture observed under the light and electron microscope after the 3- and 6-week CCl4-induced damage. The experiments were carried out in Wistar male rats. To evaluate the liver function, the test of aminophenazone elimination in the isolated perfused rat livers was used according to Miller modified by Hafte. Additionally, AspAt and AlAt activities were determined. The liver specimens were analysed under the light and electron microscope and using immunohistochemical methods. The findings show that after the 3-week CCl4-induced liver damage, IFN alpha does not significantly affect AlAt and AspAt activities, irrespective of the dose used. IFN alpha administered after the 6-week damage significantly changes those activities when the doses used are high. It was found that carbon tetrachloride does not result in evident cirrhotic changes, however it activates Ito cells, causes focal retraction of the stroma and fibrosis. The increased number of Ito cells in Disse's space observed in immunohistochemical and ultrastructural examinations is indicative of the activation of liver fibrotic processes following CCl4 administration in both variants used. IFN alpha substantially weakens fibrogenesis of the CCl4-damaged liver which is visible in the decreased number of Ito cells and weaker expression of the stroma retraction. Moreover, IFN alpha administered to the experimental animals after the CCl4-induced injury of the

  20. Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

    Science.gov (United States)

    Friques, Andreia G F; Arpini, Clarisse M; Kalil, Ieda C; Gava, Agata L; Leal, Marcos A; Porto, Marcella L; Nogueira, Breno V; Dias, Ananda T; Andrade, Tadeu U; Pereira, Thiago Melo C; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

    2015-12-30

    The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR). SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue. Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the

  1. A rat model of chronic syringomyelia induced by epidural compression of the lumbar spinal cord.

    Science.gov (United States)

    Lee, Ji Yeoun; Kim, Shin Won; Kim, Saet Pyoul; Kim, Hyeonjin; Cheon, Jung-Eun; Kim, Seung-Ki; Paek, Sun Ha; Pang, Dachling; Wang, Kyu-Chang

    2017-10-01

    OBJECTIVE There has been no established animal model of syringomyelia associated with lumbosacral spinal lipoma. The research on the pathophysiology of syringomyelia has been focused on Chiari malformation, trauma, and inflammation. To understand the pathophysiology of syringomyelia associated with occult spinal dysraphism, a novel animal model of syringomyelia induced by chronic mechanical compression of the lumbar spinal cord was created. METHODS The model was made by epidural injection of highly concentrated paste-like kaolin solution through windows created by partial laminectomy of L-1 and L-5 vertebrae. Behavioral outcome in terms of motor (Basso-Beattie-Bresnahan score) and urinary function was assessed serially for 12 weeks. Magnetic resonance images were obtained in some animals to confirm the formation of a syrinx and to monitor changes in its size. Immunohistochemical studies, including analysis for glial fibrillary acidic protein, NeuN, CC1, ED-1, and caspase-3, were done. RESULTS By 12 weeks after the epidural compression procedure, syringomyelia formation was confirmed in 85% of the rats (34 of 40) on histology and/or MRI. The syrinx cavities were found rostral to the epidural compression. Motor deficit of varying degrees was seen immediately after the procedure in 28% of the rats (11 of 40). In 13 rats (33%), lower urinary tract dysfunction was seen. Motor deficit improved by 5 weeks after the procedure, whereas urinary dysfunction mostly improved by 2 weeks. Five rats (13%, 5 of 40) died 1 month postoperatively or later, and 3 of the 5 had developed urinary tract infection. At 12 weeks after the operation, IHC showed no inflammatory process, demyelination, or accelerated apoptosis in the spinal cords surrounding the syrinx cavities, similar to sham-operated animals. CONCLUSIONS A novel experimental model for syringomyelia by epidural compression of the lumbar spinal cord has been created. The authors hope that it will serve as an important research

  2. Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

    Science.gov (United States)

    Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

    2014-01-01

    Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

  3. Increased transfer of 45Ca into brain and cerebrospinal fluid from plasma during chronic hypocalcemia in rats.

    Science.gov (United States)

    Murphy, V A; Rapoport, S I

    1988-06-28

    Recent studies have shown regulation of central nervous system [Ca] after chronic hypo- and hypercalcemia. To investigate the mechanism of this regulation, 3-week-old rats were fed diets for 8 weeks that contained low or normal levels of Ca. Plasma [Ca] was 40% less in rats fed the low Ca diet than in animals fed normal diet. Unidirectional transfer coefficients for Ca (KCa) and Cl (KCl) into cerebrospinal fluid (CSF) and brain were determined from the 10 min uptake of intravenously injected 45Ca and 36Cl in awake animals. KCa for CSF was 68% greater in low-Ca rats than in normal rats. Likewise, the values of KCa for brain regions with areas adjacent to the ventricles like the hippocampus and pons-medulla were 50% higher than in normal animals. On the other hand, KCas for parietal cortex, a brain region distant from the choroid plexus and not expected to be influenced by Ca entry into CSF, were similar between the groups. Comparison of the regional ratios of KCa/KCl revealed that a selective increase of Ca transport occurred into CSF and all brain regions except the parietal cortex in Ca-deficient rats. The results suggest that Ca homeostasis of CSF and brain [Ca] during chronic hypocalcemia is due to increased transfer of Ca from blood to brain, and that the regulation occurs via the CSF, possibly at the choroid plexus, but not via the cerebral capillaries.

  4. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    Science.gov (United States)

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-08

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  5. Impact of chronic exposure to the pesticide chlorpyrifos on respiratory parameters and sleep apnea in juvenile and adult rats.

    Directory of Open Access Journals (Sweden)

    Walaa Darwiche

    Full Text Available The widely used organophosphorus pesticide chlorpyrifos (CPF is often detected in food. CPF inhibits acetylcholinesterase and can modify muscle contractility and respiratory patterns. We studied the effects of chronic exposure to CPF on respiratory parameters and diaphragm contractility in 21- and 60-days old rats. Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups vs vehicle: controls from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle thereafter. Two developmental time points were studied: weaning (day 21 and adulthood (day 60. Whole-body plethysmography was used to score breathing patterns and apnea index during sleep. Then, diaphragm strips were dissected for the assessment of contractility and acetylcholinesterase activity. Results showed that the sleep apnea index was higher in CPF-exposed rats than in controls. In adult rats, the expiratory time and tidal volume were higher in CPF-exposed animals than in controls. At both ages, the diaphragm's amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that chronic exposure to CPF is associated with higher sleep apnea index and diaphragm contractility, and modifies respiratory patterns in sleeping juvenile and adult rats.

  6. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1983-01-01

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

  7. The effects of chronic intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats.

    Science.gov (United States)

    Patel, Sunit M; Ebenezer, Ivor S

    2008-09-28

    This study was undertaken to examine the effects of repeated administration of the GABA(B) receptor agonist baclofen on food intake in male Wistar rats. In the 1st Experiment, the effects of daily administration of physiological saline and baclofen (2 mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non-deprived rats (n=6 in each group). Baclofen significantly (P<0.05) increased cumulative food intake each day over the treatment period during the 60 min measurement period following administration. Tolerance did not develop to the short-term hyperphagic effect of baclofen over the course of the experiment. In addition, treatment with baclofen did not alter body weight of the animals over the 27 day treatment period when compared with the saline control rats. In the 2nd Experiment, the effects of acute and chronic administration of baclofen (2 mg/kg) were investigated on 24 h food intake in rats. The rats were injected daily for 21 days with either saline (n=6) or baclofen (n=6). Food intake was measured in 30 min time bins for 24 h on treatment Days 1, 12 and 21 following injection. The results showed that while baclofen produced short-term increases in food consumption following injection on treatment Days 1, 12 and 21, the daily (24 h) food intake of the animals was not significantly different from those of control rats. Thus, these data reveal that while chronic administration of baclofen (2 mg/kg) produces short-term increases in feeding without the development of tolerance, daily (24 h) food consumption is not affected. These findings are consistent with the observation that chronic administration of baclofen (2 mg/kg) had no effect on the body weight of these animals.

  8. Influence of bushenhuoxue on primary visual cortex' BDNF damage in rat model of chronic elevated intraocular pressure

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2013-04-01

    Full Text Available AIM: To observe the effect of traditional Chinese medicine(TCMof bushenhuoxue on primary visual cortex(PVCbrain-derived neurotrophic factor(BDNFin rat model of chronic elevated intraocular pressure(EIOP, and explore the mechanism of it initially. METHODS: The rat model of chronic EIOP was established by unilaterally cauterizing 3 episcleral veins, then 30 rats were divided into 3 groups randomly: control group, model group, and treatment group. After given drugs or normal saline for 8 weeks, the rats were put to death. The effect of intraocular pressure(IOP, expression of BDNF and ultrastructure of neuron cell in the PVC was observed. RESULTS: Unilaterally cauterizing episcleral veins increased IOP of the rat model obviously, there was significant difference compared with pre-operation(P<0.01. Semi-quantitative pathological analysis on PVC showed that BDNF of total area in the model group was(82438±2597.39S/μm2,mean optical density was(1155.9±123.14, integrated optical density was(12915±673.28, compared with the control group {total area was(132370±7588.47S/μm2, mean optical density was(5365±379.65, integrated optical density was(35102±2648.5}, there were statistical differences(all P<0.05,there was statistical difference in BDNF of total area between model group and treatment group{(108980±9126.77S/μm2, P<0.05}, significant difference in mean optical density between the model group and treatment group(3220.4±413.67, P<0.05, statistical difference in integrated optical density between the model group and treatment group(23821±3431.68, P<0.05. CONCLUSION: TCM of bushenhuoxue can repair the PVC damage in the rat model of chronic EIOP by enhancing expression of BDNF, improving ultrastructure of neuron cell.

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

    Science.gov (United States)

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

    2017-08-01

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

  10. Angiotensin-(1?7) inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats

    OpenAIRE

    Lu, W.; Kang, J.; Hu, K.; Tang, S.; Zhou, X.; Yu, S.; Li, Y.; Xu, L.

    2016-01-01

    Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180–200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1–7)-treated normoxia control (N-A), and Ang-(1–7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured ...

  11. Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala

    DEFF Research Database (Denmark)

    Varodayan, Florence P.; Bajo, Michal; Soni, Neeraj

    2017-01-01

    in BLA pyramidal neurons of rats exposed to 2–3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent......1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state....

  12. Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

    Science.gov (United States)

    Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

    2011-08-01

    Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults

  13. Valproate-induced hyperammonemic encephalopathy in an elderly patient with bipolar disorder

    Directory of Open Access Journals (Sweden)

    Indu Surendran

    2016-01-01

    Full Text Available Hyperammonemia is a rare side effect of valproate, diagnosis of which requires a high level of clinical suspicion. We describe a case of 57-year-old man, suffering from bipolar affective disorder, who had multiple physical comorbidities (diabetes mellitus, benign prostatic hyperplasia, hydroureteronephrosis, and chronic kidney disease and was on sodium valproate 1500 mg/day along with risperidone 6 mg/day, who developed delirium when the dose of sodium valproate was increased from 1500 mg/day to 2000 mg/day. In view of use of high doses of valproate, hyperammonemia was suspected, and on investigations, patient was found to have high ammonia levels (159 μmol/l. He was managed conservatively with stoppage of valproate and syrup lactulose. To conclude this case depicts that use of high doses of valproate can lead to hyperammonemia, especially among those with chronic medical illnesses.

  14. Chronic moderate alcohol drinking alters insulin release without affecting cognitive and emotion-like behaviors in rats.

    Science.gov (United States)

    Nelson, Nnamdi G; Suhaidi, Faten A; Law, Wen Xuan; Liang, Nu-Chu

    2017-12-16

    Because the consumption of alcoholic beverages prevails in society, its effects on diabetes risk is a subject of interest. Extant literature on this issue often disagrees. Here, we probed the effects of chronic moderate ethanol consumption on glucose metabolism in rats. The effect of chronic moderate alcohol drinking on depression- and anxiety-like behaviors and memory was also explored. Adolescent male and female Long-Evans rats consumed saccharin-sweetened 5% (1 week) and 10% ethanol (7 weeks) under a 7.5-h/day (Monday-Friday) access schedule. This exposure was followed by sucrose preference and elevated plus maze (EPM) tests during an intervening week, before a 6-week intermittent-access (Monday, Wednesday, Friday) to 20% unsweetened ethanol in a 2-bottle choice drinking paradigm was implemented (EtOH). A free-feeding control group received water (Water). Our prior work revealed that voluntary ethanol consumption decreases food intake in rats. Hence, a second control group that received water was mildly food-restricted (FR), and their average body weight was matched to that of the EtOH group. During the week following week 6 of intermittent-access to 20% ethanol, rats were submitted to sucrose preference, EPM, and novel object recognition (NOR) tests. Insulin response to a glucose load was subsequently assessed via an oral glucose tolerance test (OGTT). Rats attained and maintained blood ethanol concentrations of ∼55 mg/dL that correlated with the dose of sweetened 10% ethanol ingested. Relative to intake by Water controls, EtOH rats consumed less chow. There was no body weight difference between both groups. Neither sex of EtOH rats showed increased depression- and anxiety-like behaviors, as respectively measured by sucrose preference and EPM, nor did they show deficit in object recognition memory during abstinence. Male EtOH rats, however, showed signs of reduced general activity on the EPM. During OGTT, male EtOH rats showed a time-dependent potentiation

  15. Apple Polysaccharide inhibits microbial dysbiosis and chronic inflammation and modulates gut permeability in HFD-fed rats.

    Science.gov (United States)

    Wang, Sheng; Li, Qian; Zang, Yue; Zhao, Yang; Liu, Nan; Wang, Yifei; Xu, Xiaotao; Liu, Li; Mei, Qibing

    2017-06-01

    The saying "An apple a day keeps the doctor away" has been known for over 150 years, and numerous studies have shown that apple consumption is closely associated with reduced risks of chronic diseases. It has been well accepted that dysbiosis is the reflection of various chronic diseases. Therefore, this study investigates the effects of apple polysaccharides (AP) on gut dysbiosis. High-fat diet (HFD) fed rats were treated for 14 weeks with AP. The microbiota composition, microbiota-generated short chain fatty acids (SCFAs), gut permeability and chronic inflammation were analyzed. AP treatment showed higher abundance of Bacteroidetes and Lactobacillus while lower Firmicutes and Fusobacteium. AP significantly increased total SCFAs level that contributed by acetic acid and isobutyric acid. Moreover, AP dramatically alleviated dysbiosis-associated gut permeability and chronic inflammation with decreased plasma LBP, up-regulation of Occludin, down-regulation of tumor necrosis factor a (TNF-a), monocyte chemotactic protein 1 (MCP-1), chemokine ligand 1 (CXCL-1) and interleukin 1 beta (IL-1β). The potential mechanism is due to the fact that AP reduces gut permeability, which involves the induction of autophagy in goblet cells. Therefore, AP exerts health benefits through inhibiting gut dysbiosis and chronic inflammation and modulating gut permeability in HFD-induced dysbiosis rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Effects of chronic administration of clenbuterol on contractile properties and calcium homeostasis in rat extensor digitorum longus muscle.

    Science.gov (United States)

    Sirvent, Pascal; Douillard, Aymerick; Galbes, Olivier; Ramonatxo, Christelle; Py, Guillaume; Candau, Robin; Lacampagne, Alain

    2014-01-01

    Clenbuterol, a β2-agonist, induces skeletal muscle hypertrophy and a shift from slow-oxidative to fast-glycolytic muscle fiber type profile. However, the cellular mechanisms of the effects of chronic clenbuterol administration on skeletal muscle are not completely understood. As the intracellular Ca2+ concentration must be finely regulated in many cellular processes, the aim of this study was to investigate the effects of chronic clenbuterol treatment on force, fatigue, intracellular calcium (Ca2+) homeostasis and Ca2+-dependent proteolysis in fast-twitch skeletal muscles (the extensor digitorum longus, EDL, muscle), as they are more sensitive to clenbuterol-induced hypertrophy. Male Wistar rats were chronically treated with 4 mg.kg-1 clenbuterol or saline vehicle (controls) for 21 days. Confocal microscopy was used to evaluate sarcoplasmic reticulum Ca2+ load, Ca2+-transient amplitude and Ca2+ spark properties. EDL muscles from clenbuterol-treated animals displayed hypertrophy, a shift from slow to fast fiber type profile and increased absolute force, while the relative force remained unchanged and resistance to fatigue decreased compared to control muscles from rats treated with saline vehicle. Compared to control animals, clenbuterol treatment decreased Ca2+-transient amplitude, Ca2+ spark amplitude and frequency and the sarcoplasmic reticulum Ca2+ load was markedly reduced. Conversely, calpain activity was increased by clenbuterol chronic treatment. These results indicate that chronic treatment with clenbuterol impairs Ca2+ homeostasis and this could contribute to the remodeling and functional impairment of fast-twitch skeletal muscle.

  17. Chronic restraint stress impairs endocannabinoid mediated suppression of GABAergic signaling in the hippocampus of adult male rats.

    Science.gov (United States)

    Hu, Wen; Zhang, Mingyue; Czéh, Boldizsár; Zhang, Weiqi; Flügge, Gabriele

    2011-07-15

    Chronic stress, a risk factor for the development of psychiatric disorders, is known to induce alterations in neuronal networks in many brain areas. Previous studies have shown that chronic stress changes the expression of the cannabinoid receptor 1 (CB1) in the brains of adult rats, but neurophysiological consequences of these changes remained unclear. Here we demonstrate that chronic restraint stress causes a dysfunction in CB1 mediated modulation of GABAergic transmission in the hippocampus. Using an established protocol, adult male Sprague Dawley rats were daily restrained for 21 days and whole-cell voltage clamp was performed at CA1 pyramidal neurons. When recording carbachol-evoked inhibitory postsynaptic currents (IPSCs) which presumably originate from CB1 expressing cholecystokinin (CCK) interneurons, we found that depolarization-induced suppression of inhibition (DSI) was impaired by the stress. DSI is a form of short-term plasticity at GABAergic synapses that is known to be CB1 mediated and has been suggested to be involved in hippocampal information encoding. Chronic stress attenuated the depolarization-induced suppression of the frequency of carbachol-evoked IPSCs. Incubation with a CB1 receptor antagonist prevented this DSI effect in control but not in chronically stressed animals. The stress-induced impairment of CB1-mediated short-term plasticity at GABAergic synapses may underlie cognitive deficits which are commonly observed in animal models of stress as well as in patients with stress-related psychiatric disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Nicotine reverses anhedonic-like response and cognitive impairment in the rat chronic mild stress model of depression

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Henningsen, Kim; Bate, Simon

    2011-01-01

    Smoking rates among depressed individuals are higher than is observed in the background population, and nicotine alleviates depressive symptoms. In rodents, nicotine shows antidepressant-like effects in the forced swim and learned helplessness paradigms. Clinical depression is associated with both...... anhedonia and cognitive impairments. In rats, chronic mild stress (CMS) decreases voluntary sucrose intake, reflecting an anhedonic-like state, and impairs performance in the spontaneous alternation behaviour (SAB) test, suggesting impaired cognitive function. Here, we examine the effect of chronic...... with depression....

  19. Influence of chronic prenatal hypoxia on the specialized contact apparatus of rat heart ventricles during ontogeny

    Directory of Open Access Journals (Sweden)

    N. S. Petruk

    2014-08-01

    Full Text Available Background. During prenatal development embryonic mammalian heart undergoes deep dynamic changes due to size, structure and functions. Pathological intrauterine hypoxia influences fetal development generally and cardiogeny particularly, it affects the structure and function of the heart muscle and can lead to a variety of cardiovascular abnormalities and congenital heart defects. It is known that as a result of chronic intrauterine hypoxia during the stages of prenatal ontogeny specialized intercellular apparatus of cardiomyocytes is damaged, which plays a role not only in the mechanical connections of the cardiomyocytes, but also in the electric cooperatives, metabolic conversions, the homeostasis of the ionic balance and transport morphogenetic signaling molecules which are involved into the mechanisms of cardiogeny. It contributes to the development of diseases that may be associated with impaired local distribution of specialized intercellular junctions, and manifests as arrhythmias and cardiac conduction. Objective. To determine the effects of chronic prenatal hypoxia on the structure and distribution of specialized intercellular junctions of typical cardiomyocytes in the rat ventricular myocardium at the stages of prenatal ontogeny and to evaluate morphometric parameters of intercalated disks in the postnatal period. Materials and methods. White rats were used as a material. Intrauterine hypoxia was modelled by intraperitoneal injection of sodium nitrite from 10th to 21st day of pregnancy. Hearts were investigated by the transmission electron microscopy during the stages of prenatal and postnatal ontogeny and in adult animals. Morphometric and statistical methods were applied. Pairwise comparisons between means of different groups were performed using Student’s t-test where, for each couple of normally distributed populations, the null hypothesis that the means are equal was verified. Results. The average length of desmosomes on the 20th

  20. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

    Directory of Open Access Journals (Sweden)

    Ru-Peng Liu

    2013-01-01

    Full Text Available To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA at the auricular concha region (ACR of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS, and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA axis hyperactivity.

  1. Measurement of amino acid levels in the vitreous humor of rats after chronic intraocular pressure elevation or optic nerve transection.

    Science.gov (United States)

    Levkovitch-Verbin, Hana; Martin, Keith R G; Quigley, Harry A; Baumrind, Lisa A; Pease, Mary Ellen; Valenta, Danielle

    2002-10-01

    To investigate whether the levels of free amino acids and protein in the vitreous of rat eyes are altered with chronic intraocular pressure (IOP) elevation or after optic nerve transection. The concentrations of 20 amino acids in the vitreous humor were measured by high-performance liquid chromatography in both eyes of 41 rats with unilateral IOP elevation induced by translimbal photocoagulation. Eyes were studied 1 day and 1, 2, 4, and 9 weeks after initial IOP elevation. The same amino acids were measured in 41 rats 1 day and 2, 4, and 9 weeks after unilateral transection of the orbital optic nerve. The intravitreal protein level was assayed in additional 22 rats with IOP elevation and 12 rats after nerve transection. Two masked observers evaluated the amount of optic nerve damage with a semiquantitative, light-microscopic technique. In rats with experimental glaucoma, amino acid concentrations were unchanged 1 day after treatment. At 1 week, 4 of 20 amino acids (aspartate, proline, alanine, and lysine) were higher than in control eyes ( 0.05). Vitreous protein level was significantly higher in glaucomatous eyes than their paired controls at 1 day ( 0.01).

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  4. The behavioral effects of chronic sugar and/or caffeine consumption in adult and adolescent rats.

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    Franklin, Jane L; Wearne, Travis A; Homewood, Judi; Cornish, Jennifer L

    2017-08-01

    Caffeine is a psychostimulant frequently consumed by adults and children, often in combination with high levels of sugar. Chronic pretreatment with either substance can amplify both amphetamine and cocaine-induced hyperactivity in rodents. The present study sought to elucidate whether age at the time of exposure to sugar and/or caffeine alters sensitivity to an acute illicit psychostimulant (methamphetamine, [METH]) challenge in adulthood. Adult and adolescent (Postnatal Day 35 on first day of treatment) male Sprague-Dawley rats were treated for 26 days with water, caffeine (0.6 g/L), 10% sucrose or their combination. Locomotor behavior was measured on the first and last day of treatment. Following 9-days treatment free, animals were challenged with saline (1 ml/kg, i.p.) or METH (1 mg/kg, i.p.) and locomotor activity was measured. During the treatment period, adolescent rats maintained a higher caffeine (mg/kg) dose than their adult counterparts. Adding sugar to caffeine increased adolescent consumption and the highest caffeine dose consumed was measured in these animals. Drinking sugar-sweetened caffeinated water or combination did not produce cross-sensitization to METH administration in either age group. Nevertheless, the finding that regular exposure through adolescence to caffeinated sugar-sweetened beverages could increase consumption of caffeine and sugar later in life is important, as there is a large body of evidence that has linked excess consumption of sugar-sweetened beverages to a broad range of other negative physical and mental health outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Chronic exposure to low-levels of lead in the rat: biochemical and behavioural changes

    International Nuclear Information System (INIS)

    Rossouw, J.

    1987-01-01

    The prevalence of lead in the environment is a cause of continuing toxicology concern and there have been numerous human and animal studies to examine more thoroughly the possible consequences of exposure to this ecotoxicant. Because lead is highly toxic to the developing central nervous system, increasing concern over the rise in the lead content in the environment has been expressed. These concerns seem appropriate since more recent clinical studies have shown that prolonged exposure of children to so called 'subclinical' concentrations of lead may be associated with behavioural disorders, learning disabilities and mental retardation. Moreover, animal studies have shown that chronic perinatal low-level lead exposure elicits alterations in both learned and spontaneous behavioural patterns in the absence of typical outward signs of lead-induced neurological toxicity. No study however could relate behavioural changes to specific alterations in neurochemisty. The aim of this study was therefore to expose rats, in different stages of their development, to low-levels of lead in order to induce behavioural disorders and correlate latter with possible neurochemical changes. In accordance with the general aims of the study, the structuring of the thesis is as follows: (a) a discussion of the neurotransmitters in the brain in order to describe the different systems which have been investigated; (b) a review of appropriate literature regarding the kinetics, toxodynamics and neurotoxicity of lead and (c) a summary of the methods employed in the study. The following results are presented: (d) the effects of lead treatment on physical development of the rats; (e) the induction of behavioural supersensitivity and (f) the effects lead has on central receptors

  6. Effects of chronic estradiol treatment on the thyroid gland structure and function of ovariectomized rats

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    Elgendy Mohamed S

    2009-08-01

    Full Text Available Abstract Background Estrogen therapy is widely used nowadays in women to treat many postmenopausal symptoms but it may have some undesirable effects due to multiple organs affection. So, the aim of this study was to determine the effects of chronic estradiol treatment on the structure and function of the thyroid gland in ovarictomized rats as a model simulating menopause. Findings Thirty adult female Wistar rats divided into three groups were used in this study; the first group was sham-operated, while the second and third groups were ovariectomized. The first and second groups were injected with olive oil while the third group was injected with estradiol dipropionate daily for three months, after that; hormonal assay for T3, T4, TSH and specimens of the thyroid were taken and processed to be examined by light and electron microscopy. The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment. Histological and morphometric study in ovariectomized group revealed marked accumulation of colloid in follicular lumens with decreased epithelial height in addition to increased connective tissue amount. After estradiol treatment the follicles became smaller in size, having small amount of colloid with increased epithelial height in addition to decreased connective tissue content. Ultrastructural study supported these results in addition to the presence of large amount of intracytoplasmic colloid vesicles after estradiol treatment. Conclusion Low estrogen level may lead to mild thyroidal hypofunction while estradiol treatment may lead to hyperactivity so it should be used very cautiously in the treatment of postmenopausal symptoms to avoid its undesirable stimulatory effect on the thyroid.

  7. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    Science.gov (United States)

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  8. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

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    Ying Yang

    2017-01-01

    Full Text Available Hypoxia inducible factor 1α (HIF-1α, a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs, were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit.

  9. Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model.

    Science.gov (United States)

    Hu, Y; Niu, X; Wang, G; Huang, J; Liu, M; Peng, B

    2016-11-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were

  10. Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu

    2011-01-01

    Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

  11. The Effect of Synchronized Forced Running with Chronic Stress on Short, Mid and Long- term Memory in Rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad-Reza; Hosseini, Nasrin

    2013-03-01

    Impairment of learning and memory processes has been demonstrated by many studies using different stressors. Other reports suggested that exercise has a powerful behavioral intervention to improve cognitive function and brain health. In this research, we investigated protective effects of treadmill running on chronic stress-induced memory deficit in rats. Fifty male Wistar rats were randomly divided into five groups (n=10) as follows: Control (Co), Sham (Sh), Stress (St), Exercise (Ex) and Stress and Exercise (St & Ex) groups. Chronic restraint stress was applied by 6h/day/21days and also treadmill running at a speed 20-21m/min for 1h/day/21days. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. OUR RESULTS SHOWED THAT: 1) Although exercise alone showed beneficial effects especially on short and mid-term memory (Pshort, mid and long-term memory deficit in stressed rats. 2) Short and mid-term memory deficit was significantly (PMemory deficit in synchronized exercise with stress group was nearly similar to stressed rats. 4) Helpful effects of exercise were less than harmful effects of stress when they were associated together. The data correspond to the possibility that although treadmill running alone has helpful effects on learning and memory consolidation, but when it is synchronized with stress there is no significant benefit and protective effects in improvement of memory deficit induced by chronic stress. However, it is has a better effect than no training on memory deficit in stressed rats.

  12. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet.

    Science.gov (United States)

    Dubinion, John H; da Silva, Alexandre A; Hall, John E

    2011-04-01

    Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days. High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively). These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.

  14. Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Biernacki, Michał; Łuczaj, Wojciech; Gęgotek, Agnieszka [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland); Toczek, Marek [Department of Experimental Physiology and Pathophysiology Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok (Poland); Bielawska, Katarzyna [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland); Skrzydlewska, Elżbieta, E-mail: elzbieta.skrzydlewska@umb.edu.pl [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland)

    2016-06-15

    Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB{sub 1} receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB{sub 1} receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance in the

  15. Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood?

    Directory of Open Access Journals (Sweden)

    Namitha Nair

    2018-01-01

    Full Text Available Background: Children with seizure disorder are often treated with sodium valproate (SV on long-term basis. SV acts mainly through gamma amino butyric acid pathways, reducing the excitatory neurotransmission and modifying the monoamine concentration. Altered monoamine concentration by SV is expected to cause movement disorder and cognitive dysfunction, considered reversible after the withdrawal of treatment, but some claim it to be irreversible. It is not clear whether such adverse effects continue during adulthood. The aim of this study was to investigate whether chronic administration of SV in juvenile rats causes movement disorder and cognitive dysfunction during their early adulthood. Methods: Sixteen-day-old male Wistar rats from the central animal house, KMC, Mangalore, India in 2015, received either 200 or 400 mg/kg dose of SV for 45 consecutive days and another group served as control. Thirty days after discontinuation of the drug, at postnatal day 90, the rats were tested for movement disorder and cognitive function. Results: Chronic SV treatment in juvenile rats resulted in slow movement, tremors during adulthood but did not affect muscle tone, locomotor and exploratory activities. It also caused cognitive dysfunction in adult rats. Conclusion: Despite the reported safety of chronic SV therapy, its adverse effects such as Parkinsonism symptoms or cognitive dysfunctions should be of concern in all young patients treated with SV for many years. Persistence of cognitive impairment, tremors and generalized slow movement during adulthood after cessation of treatment that was observed in this study, warrants a close monitoring system in children who receive long-term sodium valproate.

  16. Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

    International Nuclear Information System (INIS)

    Biernacki, Michał; Łuczaj, Wojciech; Gęgotek, Agnieszka; Toczek, Marek; Bielawska, Katarzyna; Skrzydlewska, Elżbieta

    2016-01-01

    Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB 1 receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB 1 receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance in the liver of

  17. Interactive effects of chronic stress and a high-sucrose diet on nonalcoholic fatty liver in young adult male rats.

    Science.gov (United States)

    Corona-Pérez, Adriana; Díaz-Muñoz, Mauricio; Cuevas-Romero, Estela; Luna-Moreno, Dalia; Valente-Godínez, Héctor; Vázquez-Martínez, Olivia; Martínez-Gómez, Margarita; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

    2017-11-01

    Glucocorticoids have been implicated in nonalcoholic fatty liver diseases (NAFLD). The influence of a palatable diet on the response to stress is controversial. This study explored whether a high-sucrose diet could protect from hepatic steatosis induced by chronic restraint stress in young adult rats. Male Wistar rats aged 21 days were allocated into four groups (n = 6-8 per group): control, chronic restraint stress, 30% sucrose diet, and 30% sucrose diet plus chronic restraint stress. After being exposed to either tap water or sucrose solution during eight weeks, half of the rats belonging to each group were subject or not to repeated restraint stress (1 h per day, 5 days per week) during four weeks. Triacylglycerol (TAG), oxidative stress, activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), infiltration of immune cells, and glycogen amount in the liver were quantified. Serum concentrations of corticosterone and testosterone were also measured. The stressed group showed normal serum concentrations of corticosterone and did not have hepatic steatosis. However, this group showed increased glycogen, inflammation, mild fibrosis, oxidative stress, and a high activity of 11β-HSD-1 in the liver. The group exposed to the high-sucrose diet had lower concentrations of corticosterone, hepatic steatosis and moderate fibrosis. The group subject to high-sucrose diet plus chronic restraint stress showed low concentrations of corticosterone, hepatic steatosis, oxidative stress, and high concentrations of testosterone. Thus, restraint stress and a high-sucrose diet each generate different components of nonalcoholic fatty liver in young adult rats. The combination of both the factors could promote a faster development of NAFLD.

  18. Content of NCAM in the brain and pancreas of rats in response to endointoxication under conditions of experimental chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    V. A. Makarchuk

    2014-08-01

    Full Text Available The study was undertaken to examine the influence of chronic pancreatitis on the distribution of neuronal cell adhesion molecule (NCAM in the pancreas and various brain regions of rats under the conditions of endogenous intoxication. The study was conducted using 36 white nonlinear male rats (6 months old, 190–220 g. To develop the state of chronic pancreatitis, animals were subjected tolaparotomy under general anesthesia and prolonged occlusion of the pancreatic duct. The morphological examination of pancreatic tissue hasbeen performed to confirm the chronic pancreatitis development in animals. Biochemical evaluation of the pancreatic fibrosis has been performed by measuring plasma levels of hyaluronic acid, hydroxyproline and protein-free hydroxyproline. The intensity of free radical oxidation has been assessed by the change in the concentration of TBA-active products in plasma. The level of endotoxemia has been determinedby the content of average weight molecules in plasma. Protein fractions were extracted from the pancreas and various parts of the rat brain and the levels of soluble (sNCAM and membrane (mNCAM proteins were studied with the use of the competitive ELISA. Total protein in the obtained fractions was measured by the Bradford assay. Occlusion of the pancreatic duct resultedin significant atrophy of acinar tissue, fibrosis and disfunction of the pancreas along with the decreasing in the antioxidant defense of animals. The present study shows developing of endointoxication in experimentalrats, signified by considerable increase of molecules with average weight in plasma due to the activation of lipid peroxidation. It was established that, as a result of the experimental pancreas dysfunction, significant redistribution of soluble and membrane forms of NCAM took place, more especially in the cerebellum and thalamus of rats; it caused changing of cell-cell adhesion in these brain regions. Multidirectional NCAM distribution in the

  19. Chronic Carcinogenicity Study of Gasoline Vapor Condensate (GVC) and GVC Containing Methyl Tertiary-Butyl Ether in F344 Rats

    OpenAIRE

    Benson, Janet M.; Gigliotti, Andrew P.; March, Thomas H.; Barr, Edward B.; Tibbetts, Brad M.; Skipper, Betty J.; Clark, Charles R.; Twerdok, Lorraine

    2011-01-01

    Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentra...

  20. Chronic effects of soft drink consumption on the health state of Wistar rats: A biochemical, genetic and histopathological study

    OpenAIRE

    ALKHEDAIDE, ADEL; SOLIMAN, MOHAMED MOHAMED; SALAH-ELDIN, ALAA-ELDIN; ISMAIL, TAMER AHMED; ALSHEHIRI, ZAFER SAAD; ATTIA, HOSSAM FOUAD

    2016-01-01

    The present study was performed to examine the effects of chronic soft drink consumption (SDC) on oxidative stress, biochemical alterations, gene biomarkers and histopathology of bone, liver and kidney. Free drinking water of adult male Wistar rats was substituted with three different soft drinks: Coca-Cola, Pepsi and 7-Up, for three consecutive months. The serum and organs were collected for examining the biochemical parameters associated with bone, liver and kidney functions. Semi-quantitat...

  1. Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold water immersion-induced acute and chronic stress.

    Science.gov (United States)

    Juárez-Rojas, Adriana Lizbeth; García-Lorenzana, Mario; Aragón-Martínez, Andrés; Gómez-Quiroz, Luis Enrique; Retana-Márquez, María del Socorro

    2015-01-01

    Testicular apoptosis is activated by stress, but it is not clear which signaling pathway is activated in response to stress. The aim of this study was to investigate whether intrinsic, extrinsic, or both apoptotic signaling pathways are activated by acute and chronic stress. Adult male rats were subjected to cold water immersion-induced stress for 1, 20, 40, and 50 consecutive days. The seminiferous tubules:apoptotic cell ratio was assayed on acute (1 day) and chronic (20, 40, 50 days) stress. Apoptotic markers, including cleaved-caspase 3 and 8, the pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were also determined after acute and chronic stress induction. Additionally, epididymal sperm quality was evaluated, as well as corticosterone and testosterone levels. An increase in tubule apoptotic cell count percentage after an hour of acute stress and during chronic stress induction was observed. The apoptotic cells rate per tubule increment was only detected one hour after acute stress, but not with chronic stress. Accordingly, there was an increase in Bax, cleaved caspase-8 and caspase-3 pro-apoptotic proteins with a decrease of anti-apoptotic Bcl-2 in both acutely and chronically stressed male testes. In addition, sperm count, viability, as well as total and progressive motility were low in chronically stressed males. Finally, the levels of corticosterone increased whereas testosterone levels decreased in chronically stressed males. Activation of the extrinsic apoptotic pathway was shown by cleaved caspase-8 increase whereas the intrinsic apoptotic pathway activation was determined by the increase of Bax, along with Bcl-2 decrease, making evident a cross-talk between these two pathways with the activation of caspase-3. These results suggest that both acute and chronic stress can potentially activate the intrinsic/extrinsic apoptosis pathways in testes. Chronic stress also reduces the quality of epididymal spermatozoa, possibly due to a decrease in testosterone.

  2. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats

    Science.gov (United States)

    Deep, Satayanarayan; Prasad, Dipti; Singh, Shashi Bala; Khan, Nilofar

    2016-01-01

    Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state. PMID:26901349

  3. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

    Directory of Open Access Journals (Sweden)

    Neetu Kushwah

    Full Text Available Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathoge