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Sample records for conventional rats role

  1. Effects of apples and specific apple components on the cecal environment of conventional rats: Role of apple pectin

    DEFF Research Database (Denmark)

    Licht, Tine Rask; Hansen, Max; Bergström, Anders

    2010-01-01

    Background: Our study was part of the large European project ISAFRUIT aiming to reveal the biological explanations for the epidemiologically well-established health effects of fruits. The objective was to identify effects of apple and apple product consumption on the composition of the cecal...... study (14 weeks), while no effects of apple juice, puree or pomace on microbial composition in cecum were observed. Administration of either 0.33 or 3.3% apple pectin in the diet resulted in considerable changes in the DGGE profiles. A 2-fold increase in the activity of beta-glucuronidase was observed......-glucuronidase producing Clostridiales, and decreases the population of specific species within the Bacteroidetes group in the rat gut. Similar changes were not caused by consumption of whole apples, apple juice, puree or pomace....

  2. Disposition of 14C-erythritol in germfree and conventional rats

    NARCIS (Netherlands)

    Ommen, B. van; Bie, B. de; Bar, A.

    1996-01-01

    The metabolism and disposition of U-14C-erythritol was examined in four groups of three male and three female, nonfasted rats each. The rats of groups A and D were germfree; the rats of groups B and C were kept under conventional conditions. The rats of group B received an erythritol-supplemented

  3. The metabolism of 4,8-DiMeIQx in conventional and germ-free rats

    Energy Technology Data Exchange (ETDEWEB)

    Knize, M.G.; Overik, E.; Midtvedt, T.; Turteltaub, K.W.; Happe, J.A.; Gustafsson, J.A.; Felton, J.S. (Lawrence Livermore National Lab., CA (USA))

    1989-08-01

    The aromatic amine mutagen, ({sup 14}C)2-amino-3,4-8-trimethyl-imidazo(4,5-f)quinoxaline (4,8-DiMeIQx), which is derived from cooked food, was administered to conventional and germ-free AGUS rats previously fed either a semi-synthetic diet containing the cytochrome P-450 inducer beta-naphthoflavone (BNF) or a control diet without BNF. The germ-free animals had longer fecal transit times and lower induction of 7-ethoxyresorufin-O-deethylase activity than conventional rats. Induction with BNF caused a greater percentage of the radioactivity to be excreted in the feces of both germ-free and conventional rats. Feeding BNF also caused a 4-fold induction in germ-free and a 24-fold induction in conventional rat intestinal enzyme levels. Analysis of the urinary and fecal metabolites showed no consistent differences between conventional and germ-free rats in the metabolite profile. Major metabolites were identified as 8-hydroxymethyl-DiMeIQx, N-acetyl-8-hydroxymethyl-DiMeIQx, and 3-N-dimethyl-4-hydroxy-methyl-DiMeIQx. The data from this study indicate that intestinal microflora do not play a major role in the metabolism of 4,8-DiMeIQx, but the induction of intestinal enzymes does not affect the route and rate of excretion.

  4. Disposition of 14C-α-cyclodextrin in germ-free and conventional rats

    NARCIS (Netherlands)

    Ommen, B. van; Bie, A.T.H.J. de; Bär, A.

    2004-01-01

    The absorption, disposition, metabolism, and excretion of uniformly 14C-labeled α-cyclodextrin (14C-α-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, 14C-α-CD (25μCi, 50mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experi

  5. Effects of organic and conventional rice on protein efficiency ratio and pesticide residue in rats

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    Wanpen Mesomya

    2012-11-01

    Full Text Available The comparative effects of organic rice and conventional rice on the protein efficiency ratio (PER in rats were investigated by feeding 40 male Sprague-Dawley rats for four weeks with three experimental diets containing polished conventional rice (PCR, unpolished conventional rice (UCR, unpolished organic rice (UOR and a control protein diet (casein under standardised conditions. All diets were prepared according to AOAC guidelines. The results showed no statistically significant difference (P > 0.05 among the values of PER (2.75 ± 0.14 - 2.80 ± 0.09 in rats fed with diets containing PCR, UCR or UOR. Similar growth was also observed among the three groups fed with different experimental diets. Additionally, residues of pesticides, viz. carbofuran, methyl parathion, p-nitrophenol and -cyfluthrin, in rat blood and rice samples were determined using liquid chromatography–electrospray ionisation tandem mass spectrometry. Pesticide residues were not detected in all serum samples of experimental rats and only p-nitrophenol was found (8.23 ± 0.65 - 12.84 ± 2.58 mg/kg in all samples of the cooked rice diets, indicating that organic rice produced similar effect as conventional rice on PER and growth in rats.

  6. The Role of Morphosyntactic Awareness in Conventional Lexical Segmentation

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    Sandra Regina Kirchner Guimaraes

    2013-05-01

    Full Text Available Starting with the alphabetic stage of writing acquisition, the learner struggles with issues related to spelling, including the segmentation of writing in graphic words. This study examined the conventional segmentation of words and its relation to morphosyntactic awareness in a sample of students in the 4th and 5th years of elementary education in public schools. Results reveal a discrepancy between the oral identification of words and performance in the segmentation of writing, with three criteria being used by students to define “word”: (1st full meaning; (2nd sequence of letters, not only one or two; (3rd frequency of word use. Statistical analyses revealed significant positive correlations between conventional segmentation and morphosyntactic awareness. It is inferred that morphosyntactic skills support the establishment of the conventional notion of the word, and it is suggested that teachers promote the development of these skills, in order to ensure a greater command of the written language.

  7. Self-Harm and Conventional Gender Roles in Women

    Science.gov (United States)

    Straiton, Melanie L.; Hjelmeland, Heidi; Grimholt, Tine K.; Dieserud, Gudrun

    2013-01-01

    A total of thirty-two women admitted to a general hospital for medical treatment after self-harming completed measures of conventional positive and negative masculinity and femininity. Comparisons were made with two control groups with no self-harm history; 33 women receiving psychiatric outpatient treatment and a nonclinical sample of 206 women.…

  8. A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats

    OpenAIRE

    Sarai Rodríguez; Imma Raurell; Manuel Torres-Arauz; Teresa García-Lezana; Joan Genescà; María Martell

    2017-01-01

    Statins present many beneficial effects in chronic liver disease, but concerns about safety exist. We evaluated the hepatic effects of a nitric oxide-releasing atorvastatin (NCX 6560) compared to conventional statins. Simvastatin, atorvastatin and NCX 6560 were evaluated in four-week bile duct-ligated rats (BDL) simulating decompensated cirrhosis and in thirteen-week carbon tetrachloride (CCl4) intoxicated rats, a model of early cirrhosis. In the BDL model, simvastatin treated rats showed hig...

  9. Steroid balance and tissue cholesterol accumulation in germfree and conventional rats fed diets containing saturated and polyunsaturated fats.

    Science.gov (United States)

    Kellogg, T F

    1974-11-01

    Steroid balance studies were conducted on 24 conventional and 12 germfree male rats, 90-120 days old, fed diets containing either 20% safflower or 20% coconut oil. Both germfree and conventional rats fed the safflower oil diets had significantly lower serum cholesterol levels and significantly higher liver cholesterol levels than did the rats fed coconut oil. No significant differences in total fecal neutral sterols, coprostanol, Delta(7)-cholestenol, or total fecal bile acid excretion were seen between dietary groups of rats of either status. There was no evidence of qualitative differences in fecal bile acid excretion as a function of diet. The increased liver cholesterol was in the ester form, with cholesteryl linoleate the largest single component. There was no significant difference in the cholesterol content of the skin, muscle, adipose tissue, or gastrointestinal tract. The significance of a large increase in liver cholesteryl ester, lowered serum cholesterol, and no change in steroid excretion is discussed.

  10. Evaluation of right ventricle by speckle tracking and conventional echocardiography in rats with right ventricular heart failure.

    Science.gov (United States)

    Kimura, Koichi; Daimon, Masao; Morita, Hiroyuki; Kawata, Takayuki; Nakao, Tomoko; Okano, Tomoko; Lee, Seitetsu L; Takenaka, Katsu; Nagai, Ryozo; Yatomi, Yutaka; Komuro, Issei

    2015-05-13

    Speckle tracking echocardiography (STE) has been reported to be a promising technique for evaluating right ventricular (RV) function in the clinical setting. On the other hand, the usefulness of STE for RV evaluation in small animal models has not been clarified, although the rat model is among the most commonly used animal models to develop novel effective treatments against pulmonary hypertension and RV heart failure (HF).We validated the use of STE and conventional echocardiographic variables for evaluating RV functions in a rat model by comparing the echocardiographic values of RVHF rats (n = 12) induced by monocrotaline injection with those of control rats (n = 12).Most conventional echocardiographic variables demonstrated that RVHF rats have significant RV dysfunction. The area under the curve (AUC) values to distinguish RV dysfunction in RVHF rats from normal RV function in control rats using fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), RV myocardial performance index (MPI), peak tissue Doppler tricuspid annular velocities at systole (Sa), and at early diastole (Ea) were 0.71, 0.98, 0.79, 0.92, and 0.91, respectively. However, using STE analysis for RV evaluation, limited reproducibility was observed (variability 19-37 %, ICC 0.74-0.88) and the only circumferential strain showed significantly lower absolute values (P = 0.039, AUC = 0.76).To evaluate RV function in rat models, circumferential strain may be useful, however, the reproducibility and diagnostic utility were limited. Conventional echocardiographic variables such as TAPSE, tissue Doppler Sa, and Ea have superior diagnostic utility.

  11. Effect of Maternal Intake of Organically or Conventionally Produced Feed on Oral Tolerance Development in Offspring Rats

    DEFF Research Database (Denmark)

    Melballe Jensen, Maja; Halekoh, Ulrich; Stokes, Christopher

    2013-01-01

    The aim of this study was to investigate the effect of maternal consumption of organically or conventionally produced feed on immunological biomarkers and their offsprings’ response to a novel dietary antigen. First-generation rats were fed plant-based diets from two different cultivation systems...

  12. Emerging role of vesicular carriers for therapy of visceral leishmaniasis: conventional versus novel.

    Science.gov (United States)

    Kumar, Navneet; Gupta, Swati; Dube, Anuradha; Vyas, Suresh P

    2010-01-01

    Visceral leishmaniasis (VL) is a systemic protozoan infection that infects a million people living in subtropical and tropical areas. Drugs are the major treatment available against this fatal infection. Conventional chemotherapy of VL involves treatment with pen- tavalent antimonials, pentamidine, paromomycin, miltefosine, etc., but this treatment is challenging because of the failure of drugs to penetrate macrophages where the parasite hides, toxic side effects, and drug resistance due to incomplete treatment schedules. The newer therapeutic approach of combination therapy employing multi-drug combinations provides improved treatment of VL because the combination reduces length of treatment, relapse, and risk of toxicity and increases the therapeutic index. Although considerable success has been attained using combination therapies, none has yet achieved commercial status. Therefore, there is an urgent need of designing novel, site-specific leishmanicidal drug carriers for safe and effective management of VL. Colloidal carriers such as liposomes, niosomes, emulsomes, and their engineered versions offer superior therapeutic efficacy over the conventional treatment in terms of site-specific drug delivery related to absolute treatment of disease with reduced side effects and toxicity. The control over spatial and sequential distribution of drug molecules after systemic or localized administration represents the major dispute in drug-delivery systems, and this can be resolved by the use of these colloidal carriers. The present review describes current conventional and combination drug therapies with special consideration given to the emerging role of novel vesicular colloidal carriers designed against VL. Colloidal carriers employing drugs in combination could lead to reductions in the duration of conventional treatment, better patient compliance, and the prevention of anti-leishmanial drug resistance or toxicity.

  13. Effects of nano and conventional Zinc Oxide on anxiety-like behavior in male rats

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    Mozhgan Torabi

    2013-01-01

    Conclusion: Results indicate that the anxiolytic effect of ZnO NPs is much higher than its conventional form, but the introduction of ZnO NPs, as a new drug for treatment of anxiety disorder, needs further investigations.

  14. Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

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    Martin R.

    2015-08-01

    Full Text Available Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the cerebellum and other structures in the experimental group. This study, particularly in malnourished rats, demonstrates increased BOLD activation in the cerebellum.

  15. Prevalence of Food Impaction-Induced Periodontitis in Conventionally Housed Marsh Rice Rats (Oryzomys palustris).

    Science.gov (United States)

    Messer, Jonathan G; Jiron, Jessica M; Chen, Hung-Yuan; Castillo, Evelyn J; Mendieta Calle, Jorge L; Reinhard, Mary K; Kimmel, Donald B; Aguirre, J Ignacio

    2017-02-01

    Marsh rice rats (Oryzomys palustris) fed a pelleted diet high in sucrose and casein have been used as a model for moderate to severe periodontitis. Here we characterize the prevalence, location, and histopathologic features of food-impaction lesions (FIL), a unique type of oral event, in rice rats fed standard pelleted rodent chow from weaning until 34 wk of age. Healthy female rats (n = 90; age, 4 wk) were weaned into groups (n = 10 to 24) and were euthanized at 4, 16, 22, 28, or 34 wk of age. At necropsy, high-resolution photographs of the 4 jaw quadrants were examined by 3 independent observers to determine the presence, number, and location of FIL. In addition, gross periodontitis was scored (scale, 0 to 4), and the hemimaxillar surface area containing FIL was measured. Serial sections of decalcified jaws were assessed histologically. The prevalence of FIL increased with age, and was 0% (baseline), 59.1%, 69.6%, 81.8% and 80.0% in rats at age 4, 16, 22, 28, and 34 wk, respectively. FIL were predominantly located (93.9%) in the maxillary palatal surfaces of the interproximal area between molars 2 and 3 and did not affect mandibular surfaces. The percentage of the hemimaxillar surface area occupied by FIL was 6.83%, 4.82%, 2.88%, and 6.52% in rats at age 16, 22, 28, and 34 wk, respectively. Histopathologic changes in FIL varied from localized gingivitis to larger, localized periodontitis-like lesions. These data indicate that FIL are common in rice rats fed standard rodent chow, are slight to mild in severity, and are localized to specific regions in the oral cavity, thus suggesting they may be a suitable model for local maxillary periodontitis when fed standard rodent chow.

  16. Imaging in early rheumatoid arthritis: roles of magnetic resonance imaging, ultrasonography, conventional radiography and computed tomography

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Ejbjerg, Bo; Szkudlarek, Marcin

    2005-01-01

    Efficient methods for diagnosis, monitoring and prognostication are essential in early rheumatoid arthritis (RA). While conventional X-rays only visualize the late signs of preceding disease activity, there is evidence for magnetic resonance imaging (MRI) and ultrasonography being highly sensitive...... for early inflammatory and destructive changes in RA joints, and for MRI findings being sensitive to change and of predictive value for future progressive X-ray damage. Reviewing the data on X-ray, computed tomography, MRI and ultrasonography in RA, this paper discusses current and future roles...... of these imaging modalities in the management of early RA. The main focus is on recent advances in MRI and ultrasonography. Suggestions on clinical use and research priorities are provided...

  17. Dissecting a role for melanopsin in behavioural light aversion reveals a response independent of conventional photoreception.

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    Ma'ayan Semo

    Full Text Available Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT, melanopsin knockout (Opn4(-/- and rd/rd cl (melanopsin only (MO mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO mice, lacking three elements deemed essential for conventional photoreception (Opn4(-/- Gnat1(-/- Cnga3(-/-. Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice.

  18. Comparative inflammatory effect of antiseptic irrigating solutions against conventional irrigation with sodium chloride in rats.

    OpenAIRE

    Rodríguez Alfaro, Miguel; Profesor Asociado del Departamento Académico de Ciencias Básicas de la Facultad de Odontología de la UNMSM.; Chumpitaz Cerrate, Víctor; Profesor Auxiliar del Departamento Académico de Ciencias Básicas de la Facultad de Odontología de la UNMSM.; Burga Sánchez, Jonny; Profesor Auxiliar del Departamento Académico de Ciencias Básicas de la Facultad de Medicina de la UCSUR.; Arroyo Acevedo, Jorge; Profesor Principal del Departamento Académico de Ciencias Básicas de la Facultad de Medicina de la UNMSM.; Ramón Rosales, Jorge; Profesor Auxiliar del departamento Académico de Ciencias Básicas de la Facultad de Estomatología de la UCSUR.; Aguirre Siancas, Elías; Profesor Auxiliar del Departamento Académico de Ciencias Básicas de la Facultad de Odontología de la UNMSM.; Cabrejos Álvarez, José; Profesor de la Catedra de Cirugia Bucal y Máxilofacial de la Facultad de Estomatología de la UIGV.; Zegarra Cuya, Juan; Ex-Profesor del Departamento Académico de Ciencias Básicas de la Facultad de Odontología de la UNMSM.

    2014-01-01

    The aim of this study was to demonstrate that the use of irrigating solutions in surgical procedures does not alter both inflammation processes and tissue repair. Four (04) groups were formed containing 15 rats each. After being dosed with general anaesthesia, they underwent osteotomy in the tibia with tungsten carbide burs and irrigation for 15 seconds, using the following solutions in each group: A) 0,12 % chlorhexidine with cetylpyridinium 0,05 %, B) 0,12 % chlorhexidine with aspartame; C)...

  19. Effects of conventional anticonvulsant drugs on generalized tonic-clonic seizures in Noda epileptic rats.

    Science.gov (United States)

    Inoue, Maki; Yamamoto, Ayaka; Kaneko, Yuka; Noda, Atsushi; Naito, Hiroyuki

    2014-09-01

    Noda epileptic rats (NERs) present with clinico-pathological manifestations reminiscent of human generalized tonic-clonic epilepsy. Thus, this strain of rat has been a model of primary, generalized, tonic-clonic epilepsy. However, the infrequency of seizures in these rats makes the assessment of antiepileptic drugs (AEDs) difficult. Therefore, traditional AEDs have only been tested in NERs against audiogenic seizures evoked by weekly acoustic priming from 3 to 22 weeks of age or by using the kindling procedure in adult animals. Adult NERs are susceptible to changes in their environment, such as bedding replacement or unpleasant sensory stimuli. In the present study, traditional AEDs-phenobarbital (PB) and sodium valproate (VPA)-were evaluated against seizures evoked by strong environmental stimuli in mature NERs that had not been previously primed. The number of animals presenting with seizures decreased in a dose-dependent manner following administration of either PB (dose range 1.0-5.0mg/kg) or VPA (50 and 100mg/kg). Consequently, the utility of NERs as a model of generalized tonic-clonic epilepsy was confirmed. This type of protocol can be used to further evaluate AEDs and test effects of chronic administration of AEDs. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Hepatoprotective and Antioxidant Potential of Organic and Conventional Grape Juices in Rats Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Iselde Buchner

    2014-04-01

    Full Text Available The objective of this study was to investigate the antioxidant and hepatoprotective effect of the chronic use of conventional (CGJ or organic (OGJ grape juice from the Bordeaux variety grape on oxidative stress and cytoarchitecture in the liver of rats supplemented with a high-fat diet (HFD for three months. The results demonstrated that HFD induced an increase in thiobarbituric acid-reactive substances (TBARS, catalase (CAT activity and 2′,7′-dihydrodichlorofluorescein (DCFH oxidation and a decrease in sulfhydryl content and superoxide dismutase (SOD and glutathione peroxidase (GPx activities. HFD also induced hepatocellular degeneration and steatosis. These alterations were prevented by CGJ and OGJ, where OGJ was more effective. Therefore, it was concluded that HFD induced oxidative stress and liver damage and that the chronic use of grape juice was able to prevent these alterations.

  1. Comparative evaluation of the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods.

    Science.gov (United States)

    Devgan, Manish; Nanda, Arun; Ansari, Shahid Husain

    2013-09-01

    The aim of the present study was to assess the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods. Aqueous and ethanol extracts of Pterocarpus marsupium heartwood were prepared by conventional methods (infusion, decoction, maceration and percolation) and non conventional methods, such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE). The crude aqueous extracts were administered orally to both normal and alloxan induced male albino rats (Sprague-Dawley strain). The experimental set up consisted of 48 male albino rats divided into 6 groups: Normal control, diabetic control (sterile normal saline, 1 ml/100 g body weight), standard (gliclazide, 25 mg/1000g of body weight), groups 4-6 (crude aqueous percolation, optimized UAE and MAE extract, 250 mg/1000g of body weight). In acute treatment, the reduction of blood glucose level was statistically significant with the oral administration of UAE and percolation aqueous extracts to the hyperglycemic rats. In sub-acute treatment, the UAE aqueous extract led to consistent and statistically significant (p<0.001) reduction in the blood glucose levels. There was no abnormal change in body weight of the hyperglycemic animals after 10 days of administration of plant extracts and gliclazide. This study justifies the traditional claim and provides a rationale for the use of Pterocarpus marsupium to treat diabetes mellitus. The antidiabetic activity of Pterocarpus marsupium can be enhanced by extracting the heartwood by non conventional method of UAE.

  2. q-space and conventional diffusion imaging of axon and myelin damage in the rat spinal cord after axotomy.

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    Farrell, Jonathan A D; Zhang, Jiangyang; Jones, Melina V; Deboy, Cynthia A; Hoffman, Paul N; Landman, Bennett A; Smith, Seth A; Reich, Daniel S; Calabresi, Peter A; van Zijl, Peter C M

    2010-05-01

    Parallel and perpendicular diffusion properties of water in the rat spinal cord were investigated 3 and 30 days after dorsal root axotomy, a specific insult resulting in early axonal degeneration followed by later myelin damage in the dorsal column white matter. Results from q-space analysis (i.e., the diffusion probability density function) obtained with strong diffusion weighting were compared to conventional anisotropy and diffusivity measurements at low b-values, as well as to histology for axon and myelin damage. q-Space contrasts included the height (return to zero displacement probability), full width at half maximum, root mean square displacement, and kurtosis excess of the probability density function, which quantifies the deviation from gaussian diffusion. Following axotomy, a significant increase in perpendicular diffusion (with decreased kurtosis excess) and decrease in parallel diffusion (with increased kurtosis excess) were found in lesions relative to uninjured white matter. Notably, a significant change in abnormal parallel diffusion was detected from 3 to 30 days with full width at half maximum, but not with conventional diffusivity. Also, directional full width at half maximum and root mean square displacement measurements exhibited different sensitivities to white matter damage. When compared to histology, the increase in perpendicular diffusion was not specific to demyelination, whereas combined reduced parallel diffusion and increased perpendicular diffusion was associated with axon damage. (c) 2010 Wiley-Liss, Inc.

  3. Comprehending Speaker Intent in Rebuttal Analogy Use: The Role of Irony Mapping, Absurdity Comparison and Argumentative Convention.

    Science.gov (United States)

    Colston, Herbert L.

    2000-01-01

    Investigated the role that irony mapping, absurdity comparison, and argumentative convention play in interpreters' derivations of speaker's intentions in using rebuttal analogies. Three rebuttal types were rated on argumentativeness and social attack in verbal conflict and nonverbal conflict scenarios. Results found that analogies with ironic…

  4. Increased angiogenesis in portal hypertensive rats: role of nitric oxide.

    Science.gov (United States)

    Sumanovski, L T; Battegay, E; Stumm, M; van der Kooij, M; Sieber, C C

    1999-04-01

    Systemic and especially splanchnic arterial vasodilation accompany chronic portal hypertension. Different soluble mediators causing this vasodilation have been proposed, the strongest evidence being for nitric oxide (NO). No data exist if structural vascular changes may partly account for this vasodilatory state. Here, we developed a new in vivo quantitative angiogenesis assay in the abdominal cavity and determined if: 1) portal hypertensive rats show increased angiogenesis; and 2) angiogenesis is altered by inhibiting NO formation. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls (CON). During the index operation (day 0), a teflon ring filled with collagen I (Vitrogen 100) was sutured in the mesenteric cavity. After 16 days, rings were explanted, embedded in paraffin, and ingrown vessels counted using a morphometry system. The role of NO was tested by adding an antagonist of NO formation (Nomega-nitro-L-arginine [NNA], 3.3 mg/kg/d) into the drinking water. The mean number of ingrown vessels per implant was significantly higher in PVL rats compared with CON rats, i.e., 1,453 +/- 187 versus 888 +/- 116, respectively (P <.05; N = 5 per group). NNA significantly (P <.01) inhibited angiogenesis in PVL (202 +/- 124; N = 5) and in CON (174 +/- 25; N = 6) rats, respectively. In contrast, the beta-adrenergic blocker, propranolol, did not prevent angiogenesis either in PVL or CON rats in a separate set of experiments (data not shown). The conclusions drawn from this study are that: 1) rats with portal hypertension show increased angiogenesis; and 2) inhibition of NO formation significantly prevents angiogenesis in both PVL and CON rats. Therefore, splanchnic vasodilation in chronic portal hypertension may also be a result of structural changes.

  5. Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E

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    Mona Abdullah Al-Damegh

    2012-07-01

    Full Text Available OBJECTIVE: The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. MATERIALS AND METHODS: The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day or electromagnetic field plus vitamin E (2.7 mg/kg/day. All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. RESULTS: There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. CONCLUSION: Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes.

  6. The Role of Conventional Ultrasound in the Assessment of Thyroid Nodule in Erbil City

    Science.gov (United States)

    Musa, Sarbast Ismail; Hanary, Salah Mohammad

    2016-01-01

    Background: Nodular thyroid disease is relatively common although thyroid cancer is rare. The aim of this study is to evaluate the advantage and reliability of conventional ultrasound in correlating sonographic characteristics of thyroid nodule with US-FNAC guided result as a diagnostic aid in thyroid nodule. Method: 111 patients were examined by…

  7. Reinforcing the role of the conventional C-arm - a novel method for simplified distal interlocking

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    Windolf Markus

    2012-01-01

    Full Text Available Abstract Background The common practice for insertion of distal locking screws of intramedullary nails is a freehand technique under fluoroscopic control. The process is technically demanding, time-consuming and afflicted to considerable radiation exposure of the patient and the surgical personnel. A new concept is introduced utilizing information from within conventional radiographic images to help accurately guide the surgeon to place the interlocking bolt into the interlocking hole. The newly developed technique was compared to conventional freehand in an operating room (OR like setting on human cadaveric lower legs in terms of operating time and radiation exposure. Methods The proposed concept (guided freehand, generally based on the freehand gold standard, additionally guides the surgeon by means of visible landmarks projected into the C-arm image. A computer program plans the correct drilling trajectory by processing the lens-shaped hole projections of the interlocking holes from a single image. Holes can be drilled by visually aligning the drill to the planned trajectory. Besides a conventional C-arm, no additional tracking or navigation equipment is required. Ten fresh frozen human below-knee specimens were instrumented with an Expert Tibial Nail (Synthes GmbH, Switzerland. The implants were distally locked by performing the newly proposed technique as well as the conventional freehand technique on each specimen. An orthopedic resident surgeon inserted four distal screws per procedure. Operating time, number of images and radiation time were recorded and statistically compared between interlocking techniques using non-parametric tests. Results A 58% reduction in number of taken images per screw was found for the guided freehand technique (7.4 ± 3.4 (mean ± SD compared to the freehand technique (17.6 ± 10.3 (p p = 0.001. Operating time per screw (from first shot to screw tightened was on average 22% reduced by guided freehand (p = 0

  8. A possible physiological role of taurine in the adult female rat liver

    National Research Council Canada - National Science Library

    Pierre, Y; Chatagner, F

    1981-01-01

    ...) in the liver of the lactating rat: 1.84 twenty-one days after the birth of pups. These observations suggest a physiological role for the higher concentration of taurine in the liver of the adult female rat...

  9. Chronic gastritis rat model and role of inducing factors

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  10. Possible role for cryoballoon ablation of right atrial appendage tachycardia when conventional ablation fails.

    Science.gov (United States)

    Amasyali, Basri; Kilic, Ayhan

    2015-06-01

    Focal atrial tachycardia arising from the right atrial appendage usually responds well to radiofrequency ablation; however, successful ablation in this anatomic region can be challenging. Surgical excision of the right atrial appendage has sometimes been necessary to eliminate the tachycardia and prevent or reverse the resultant cardiomyopathy. We report the case of a 48-year-old man who had right atrial appendage tachycardia resistant to multiple attempts at ablation with use of conventional radiofrequency energy guided by means of a 3-dimensional mapping system. The condition led to cardiomyopathy in 3 months. The arrhythmia was successfully ablated with use of a 28-mm cryoballoon catheter that had originally been developed for catheter ablation of paroxysmal atrial fibrillation. To our knowledge, this is the first report of cryoballoon ablation without isolation of the right atrial appendage. It might also be an alternative to epicardial ablation or surgery when refractory atrial tachycardia originates from the right atrial appendage.

  11. Role of conventional therapies in the era of biological treatment in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Paolo Gionchetti; Fernando Rizzello; Carlo Calabrese; Rosy Tambasco; Ramona Brugnera; Giulia Straforini; Giuseppina Liguori; Giulia Spuri Fornarini; Donatella Riso; Massimo Campieri

    2011-01-01

    Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts.Numerous controlled trials have been performed in CD.This review concentrates on the results of randomized, placebo-controlled trials, and meta-analyses when available, that provide the highest degree of evidence.Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase.The advent of biological drugs has opened new therapeutic horizons for treating CD, modifying the treatment goals.However, the large majority of patients with CD will be managed through conventional therapy, even if they are a prelude to biological therapy.

  12. The role of co-located storage for wind power producers in conventional electricity markets

    KAUST Repository

    Bitar, E.

    2011-06-01

    In this paper we study the problem of optimizing contract offerings for an independent wind power producer (WPP) participating in conventional day-ahead forward electricity markets for energy. As wind power is an inherently variable source of energy and is difficult to predict, we explore the extent to which co-located energy storage can be used to improve expected profit and mitigate the the financial risk associated with shorting on the offered contracts. Using a simple stochastic model for wind power production and a model for the electricity market, we show that the problem of determining optimal contract offerings for a WPP with co-located energy storage can be solved using convex programming.

  13. Organic and Conventional Yerba Mate (Ilex paraguariensis A. St. Hil Improves Metabolic Redox Status of Liver and Serum in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Cátia S. Branco

    2013-07-01

    Full Text Available Organic and conventional yerba mate (Ilex paraguariensis is widely used in South America to prepare nonalcoholic drinks rich in polyphenols. These compounds are able to prevent the generation of reactive species, thus minimizing the incidence of several diseases. In this perspective, we hypothesized that yerba mate may have protective effects against pentylenetetrazol (PTZ-induced oxidative damage in liver and serum of rats. Animals (n = 42 received distilled water (control or yerba mate (organic or conventional for fifteen days. Then, half of the rats of each group received 60 mg/kg PTZ intraperitoneally or saline solution. After 30 min the animals were euthanized and the liver and blood were collected. The results showed that organic and conventional yerba mate avoided PTZ-induced oxidative damage and nitric oxide production in the liver and serum of the rats. Moreover, both kinds of yerba mate prevented the decrease in enzymatic (superoxide dismutase and catalase and non-enzymatic (sulfhydryl protein content defenses in the liver and serum. In addition, histopathologic analysis of the liver showed that yerba mate reduced PTZ-induced cell damage. These findings indicate that yerba mate provides hepatoprotection and improves antioxidant status in the serum, which may contribute to the development of new therapeutic strategies using nutraceuticals drinks.

  14. Effects of nonhypotensive endotoxemia in conscious rats: Role of prostaglandins

    Energy Technology Data Exchange (ETDEWEB)

    Burnier, M.; Waeber, B.; Aubert, J.F.; Nussberger, J.; Brunner, H.R. (Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland))

    1988-03-01

    A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin. However, a marked increase in plasma renin activity plasma epinephrine and plasma norepinephrine was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow, and an increase in coronary blood flow were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevent the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension. The humoral but not the vascular effects of endotoxemia were abolished when prostaglandin synthesis was inhibited.

  15. Role of mitochondrial damage during cardiac apoptosis in septic rats

    Institute of Scientific and Technical Information of China (English)

    LI Li; HU Bang-chuan; CHEN Chang-qin; GONG Shi-jin; YU Yi-hua; DAI Hai-wen; YAN Jing

    2013-01-01

    Background Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression.However,the underlying mechanism remains unknown.This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats.Methods Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection.Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy.In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis.Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage.Oxidative stress was assessed by mitochondrial lipid and protein oxidation,and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity.Results Sepsis-induced inflammatory cell infiltration,myocardium degeneration and dropsy were time-dependent.Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge.Compared with sham-treated rats,the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours,12 hours and 24 hours post-injection (P < 0.05).The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis,indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B.Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner.Both superoxide dismutase and glutathione peroxidase activities decreased,while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge.Conclusions Septic challenge induced

  16. The Role of Pharmacomechanical Endovascular Intervention for Iliofemoral Vein Thrombosis Compared to Conventional Anticoagulation Therapy.

    Science.gov (United States)

    Kim, In Sub; Jo, Won Min

    2017-01-01

    Although anticoagulation therapy is the primary treatment for deep vein thrombosis (DVT), it has not been associated with the rapid recanalization of the venous occlusion. Moreover, it is associated with long-term disability due to post-thrombotic syndrome (PTS). In contrast, pharmacomechanical endovascular intervention (PMI) results in more rapid clinical improvement in DVT patients, but there are few reports on its long-term outcomes. This retrospective study evaluated the clinical effectiveness of PMI compared to conventional anticoagulation therapy (ACA) for acute and subacute iliofemoral DVT. We reviewed the medical records of 102 patients with iliofemoral DVT. A total of 46 patients for ACA and 56 patients for PMI were enrolled. We analyzed the clinical differences between the PMI and ACA groups by comparing the clinical signs, residual DVT free-rate, and PTS-free rate. There were no statistically significant differences in the demographic characteristics and risk factors except age between the groups (age: ACA, 52.0 ± 18.0 years; PMI, 59.0 ± 17.0 years; P = 0.035). The 1-, 3-, and 5-year residual DVT-free rate (ACA = 84.7%, 71.6%, and 46.0%; PMI = 82.1%, 76.8%, and 76.8%, respectively; P = 0.235) was not significantly different. However, the 1-, 3-, and 5-year PTS-free rate was significantly different (ACA = 93.5%, 74.0%, and 55.7%; PMI = 92.9%, 90.0%, and 90.0%, respectively; P = 0.019). There was no significant difference in the rate of other complications. PMI showed a lower incidence of PTS during the follow-up period. Therefore, PMI should be considered as an effective therapeutic modality for patients with iliofemoral DVT.

  17. Role of collagen fibers in acupuncture analgesia therapy on rats.

    Science.gov (United States)

    Yu, Xiaojia; Ding, Guanghong; Huang, Hong; Lin, Jun; Yao, Wei; Zhan, Rui

    2009-01-01

    Acupuncture, a traditional Chinese therapeutic technique, has been put into practice for more than 4000 years and widely used for pain management since 1958. However, what is the mechanism underlying the acupuncture for analgesia effects by stimulation of acupoints, what substances receive the original mechanical acupuncture signals from the acupoints, or what transforms these signals into effective biological signals are not well understood. In this work, the role of collagen fibers at acupoints during acupuncture analgesia on rats was investigated. When the structure of the collagen fibers at Zusanli (ST36) was destroyed by injection of type I collagenase, the needle force caused by the acupuncture declined and the analgesic effects of rotation or lift-thrusting manipulations was attenuated accompanying the restraint of the degranulation ratios of mast cells. We propose that collagen fibers play an important role in acupuncture-induced analgesia, and they participate in signal transmission and transform processes.

  18. Phosphine-induced oxidative damage in rats: role of glutathione.

    Science.gov (United States)

    Hsu, Ching-Hung; Chi, Bei-Ching; Liu, Ming-Yie; Li, Jih-Heng; Chen, Chiou-Jong; Chen, Ruey-Yu

    2002-09-30

    Phosphine (PH(3)), generated from aluminium, magnesium and zinc phosphide, is a widely used pesticide. PH(3) induces oxidative stress in insects, mammalian cells, animals, and humans. The involvement of glutathione (GSH) in PH(3)-induced oxidative toxicity is controversial. GSH levels in various tested tissues were reduced in aluminium phosphide-poisoned rats and humans, while the levels remained unchanged in insects and mammalian cells. This study examines the effectiveness of endogenous GSH as a protective agent against PH(3)-induced oxidative damage in rats. The association of PH(3)-induced nephrotoxicity and cardiotoxicity with free radical production was also tested. Male Wistar rats, administered intraperitoneally (I.P.) with PH(3) at 4 mg/kg, were evaluated 30 min after treatment for PH(3) toxicity to organs. PH(3) significantly decreased GSH, GSH peroxidase and catalase, while significantly increased lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals), DNA oxidation (as 8-hydroxydeoxyguaonsoine) and superoxide dismutase (SOD) levels in kidney and heart. These changes were significantly alleviated by melatonin (10 mg/kg I.P., 30 min before PH(3)), with the exception of SOD activity in heart tissue. The study also found that buthionine sulfoximine (1 g/kg I.P., 24 h before PH(3)) significantly enhanced the effect of PH(3) on GSH loss and lipid peroxidation elevation in lung. These findings indicate that (1) endogenous GSH plays a crucial role as a protective factor in modulating PH(3)-induced oxidative damage, and (2) PH(3) could injure kidney and heart (as noted earlier with brain, liver and lung) via oxidative stress and the antioxidant melatonin effectively prevents the damage.

  19. The Forgotten Virulence Factor: The 'non-conventional' Hemolysin TlyA And Its Role in Helicobacter pylori Infection.

    Science.gov (United States)

    Javadi, Mohammad Bagher; Katzenmeier, Gerd

    2016-12-01

    Helicobacter pylori is a human-specific Gram-negative pathogenic bacterium which colonizes the gastric mucosal layer in the stomach causing diseases such as peptic ulcer, adenocarcinoma, and gastric lymphoma. It is estimated that approximately half of the world's population is infected with H. pylori making it the most intensively characterized microbial pathogen up to now. Hemolysis has been suggested to significantly contribute to colonization of the stomach and disease progression by H. pylori. In a number of earlier studies, TlyA was characterized as a putative pore-forming cytolysin. Although a few observations in the literature suggest a role for TlyA as significant virulence factor of H. pylori, the molecular and structural characterization of this protein is much curtailed at present. Given the intensive characterization of numerous H. pylori virulence factors over the past decade, surprisingly little information exists for the TlyA toxin and its significance for pathogenesis. This review provides a brief overview on microbial hemolysis and its role for pathogenesis and discusses recent research efforts aimed at an improved understanding of the role of the 'non-conventional' hemolysin and its associated RNA methyltransferase TlyA from H. pylori.

  20. ROLE OF THE SEROTONIN IN MEMORY PROCESSES IN THE RAT

    Directory of Open Access Journals (Sweden)

    Andreea Ioana Hefco

    2005-08-01

    Full Text Available Chronic 5, 7-dihydroxytryptamine (5, 7-DHT, 150 μg,i.c.v. disruption of the central serotonergic function, is able to interfere with learning and memory processes in the rat. Serotonin depletion significantly diminished spontaneous alternation % in Y-maze task, which suggest the impairment of short-term memory. Long-term memory does not undergo significant changes. Parachlorophenylalanine (200μg i.c.v. x 3 days a semichronic serotonin neurotoxin, do not impaired long-term memory. This effect of serotonin depletion was not produced at the level of organism motricity that, in turn, would allow an enhancing efficiency of another neurotransmitters contribution to memory processes, as number of arm entries was not affected by serotonin depletion. It is concluded that learning and memory processes is a multitransmitter system function, in which serotonin play an important role

  1. Role of the vomeronasal organ on the estral cycle reduction by pheromones in the rat.

    Science.gov (United States)

    Mora, O A; Sánchez-Criado, J E; Guisado, S

    1985-09-01

    The role of he vomeronasal organ on the estral cycle reduction induced by pheromones is studied in adult female wistar rats. The animals were divided in three groups: I, intact rats; II, vomeronasalectomized rats (VNX); and III, sham operated rats (sham). Each group was submitted to another three distinct conditions from the day they were weaned (21 days old): Isolated female rats; with male odors from two adult males of tested sexual potency, and isolated rats again. The isolated intact rats show mainly 5 day length cycles. The groups I and III (intacts and sham) with male odors, show 4 day length cycles. The VNX animals show 5 day cycles in any one experimental conditions. These results support the idea that the vomeronasal organ is the receptor of the male reducing cycle pheromone in the female rat.

  2. Interrogating the Conventional Boundaries of Research Methods in Social Sciences: The Role of Visual Representation in Ethnography

    Directory of Open Access Journals (Sweden)

    Nel Glass

    2008-05-01

    Full Text Available The author will propose that the use of performative social science is a means to deliberately interrogate long held conventions of established research. The innovative role of visual art representation in data collection, analysis and public engagement with research will be discussed. Examples will be drawn from two postmodern feminist ethnographic research which investigated academic professional development, resilience, hope and optimism in the UK, US, Australia and New Zealand from 1997-2005. Artwork was initially created as data collection and digitalised as representation to intentionally validate the voices of research participants, the researcher and viewers of the work. The research participants and viewers were given opportunities to actively engage with the visual work. Artwork complimented two additional research methods: critical conversational interviewing and reflective journaling. This paper will address the ways inclusion of art methods contributed and deepened data representation. The role of crafting artwork in the field, the artistic changes that represented the complexity of data analysis and engagement with the work will be explored. It will be argued that the creation and engagement with artwork in research is an empowering and dynamic process for researchers and participants. It is an innovative means of representing intersubjectivity that results in reciprocity. URN: urn:nbn:de:0114-fqs0802509

  3. Clinical and anatomic pathology effects of serial blood sampling in rat toxicology studies, using conventional or microsampling methods.

    Science.gov (United States)

    Caron, Alexis; Lelong, Christine; Bartels, T; Dorchies, O; Gury, T; Chalier, Catherine; Benning, Véronique

    2015-08-01

    As a general practice in rodent toxicology studies, satellite animals are used for toxicokinetic determinations, because of the potential impact of serial blood sampling on toxicological endpoints. Besides toxicological and toxicokinetic determinations, blood samples obtained longitudinally from a same animal may be used for the assessment of additional parameters (e.g., metabolism, pharmacodynamics, safety biomarkers) to maximize information that can be deduced from rodents. We investigated whether removal of up to 6 × 200 μL of blood over 24h can be applied in GLP rat toxicology studies without affecting the scientific outcome. 8 week-old female rats (200-300 g) were dosed for up to 1 month with a standard vehicle and subjected or not (controls) to serial blood sampling for sham toxicokinetic/ancillary determinations, using miniaturized methods allowing collection of 6 × 50, 100 or 200 μL over 24h. In-life endpoints, clinical pathology parameters and histopathology of organs sensitive to blood volume reduction were evaluated at several time points after completion of sampling. In sampled rats, minimal and reversible changes in red blood cell mass (maximally 15%) and subtle variations in liver enzymes, fibrinogen and neutrophils were not associated with any organ/tissue macroscopic or microscopic correlate. Serial blood sampling (up to 6 × 200 μL over 24h) is compatible with the assessment of standard toxicity endpoints in adult rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Auxin/AID versus conventional knockouts: distinguishing the roles of CENP-T/W in mitotic kinetochore assembly and stability.

    Science.gov (United States)

    Wood, Laura; Booth, Daniel G; Vargiu, Giulia; Ohta, Shinya; deLima Alves, Flavia; Samejima, Kumiko; Fukagawa, Tatsuo; Rappsilber, Juri; Earnshaw, William C

    2016-01-01

    Most studies using knockout technologies to examine protein function have relied either on shutting off transcription (conventional conditional knockouts with tetracycline-regulated gene expression or gene disruption) or destroying the mature mRNA (RNAi technology). In both cases, the target protein is lost at a rate determined by its intrinsic half-life. Thus, protein levels typically fall over at least 1-3 days, and cells continue to cycle while exposed to a decreasing concentration of the protein. Here we characterise the kinetochore proteome of mitotic chromosomes isolated from a cell line in which the essential kinetochore protein CENP-T is present as an auxin-inducible degron (AID) fusion protein that is fully functional and able to support the viability of the cells. Stripping of the protein from chromosomes in early mitosis via targeted proteasomal degradation reveals the dependency of other proteins on CENP-T for their maintenance in kinetochores. We compare these results with the kinetochore proteome of conventional CENP-T/W knockouts. As the cell cycle is mostly formed from G1, S and G2 phases a gradual loss of CENP-T/W levels is more likely to reflect dependencies associated with kinetochore assembly pre-mitosis and upon entry into mitosis. Interestingly, a putative super-complex involving Rod-Zw10-zwilch (RZZ complex), Spindly, Mad1/Mad2 and CENP-E requires the function of CENP-T/W during kinetochore assembly for its stable association with the outer kinetochore, but once assembled remains associated with chromosomes after stripping of CENP-T during mitosis. This study highlights the different roles core kinetochore components may play in the assembly of kinetochores (upon entry into mitosis) versus the maintenance of specific components (during mitosis).

  5. Advancing the right to health through global organizations: The potential role of a Framework Convention on Global Health.

    Science.gov (United States)

    Friedman, Eric A; Gostin, Lawrence O; Buse, Kent

    2013-06-14

    Organizations, partnerships, and alliances form the building blocks of global governance. Global health organizations thus have the potential to play a formative role in determining the extent to which people are able to realize their right to health. This article examines how major global health organizations, such as WHO, the Global Fund to Fight AIDS, TB and Malaria, UNAIDS, and GAVI approach human rights concerns, including equality, accountability, and inclusive participation. We argue that organizational support for the right to health must transition from ad hoc and partial to permanent and comprehensive. Drawing on the literature and our knowledge of global health organizations, we offer good practices that point to ways in which such agencies can advance the right to health, covering nine areas: 1) participation and representation in governance processes; 2) leadership and organizational ethos; 3) internal policies; 4) norm-setting and promotion; 5) organizational leadership through advocacy and communication; 6) monitoring and accountability; 7) capacity building; 8) funding policies; and 9) partnerships and engagement. In each of these areas, we offer elements of a proposed Framework Convention on Global Health (FCGH), which would commit state parties to support these standards through their board membership and other interactions with these agencies. We also explain how the FCGH could incorporate these organizations into its overall financing framework, initiate a new forum where they collaborate with each other, as well as organizations in other regimes, to advance the right to health, and ensure sufficient funding for right to health capacity building. We urge major global health organizations to follow the leadership of the UN Secretary-General and UNAIDS to champion the FCGH. It is only through a rights-based approach, enshrined in a new Convention, that we can expect to achieve health for all in our lifetimes.

  6. The role of non-governmental organizations in global health diplomacy: negotiating the Framework Convention on Tobacco Control.

    Science.gov (United States)

    Lencucha, Raphael; Kothari, Anita; Labonté, Ronald

    2011-09-01

    The Framework Convention on Tobacco Control (FCTC) is an exemplar result of global health diplomacy, based on its global reach (binding on all World Health Organization member nations) and its negotiation process. The FCTC negotiations are one of the first examples of various states and non-state entities coming together to create a legally binding tool to govern global health. They have demonstrated that diplomacy, once consigned to interactions among state officials, has witnessed the dilution of its state-centric origins with the inclusion of non-governmental organizations (NGOs) in the diplomacy process. To engage in the discourse of global health diplomacy, NGO diplomats are immediately presented with two challenges: to convey the interests of larger publics and to contribute to inter-state negotiations in a predominantly state-centric system of governance that are often diluted by pressures from private interests or mercantilist self-interest on the part of the state itself. How do NGOs manage these challenges within the process of global health diplomacy itself? What roles do, and can, they play in achieving new forms of global health diplomacy? This paper addresses these questions through presentation of findings from a study of the roles assumed by one group of non-governmental actors (the Canadian NGOs) in the FCTC negotiations. The findings presented are drawn from a larger grounded theory study. Qualitative data were collected from 34 public documents and 18 in-depth interviews with participants from the Canadian government and Canadian NGOs. This analysis yielded five key activities or roles of the Canadian NGOs during the negotiation of the FCTC: monitoring, lobbying, brokering knowledge, offering technical expertise and fostering inclusion. This discussion begins to address one of the key goals of global health diplomacy, namely 'the challenges facing health diplomacy and how they have been addressed by different groups and at different levels of

  7. Comparative Study of High Powerful Magnet with Conventional Repair of Suture in the Intestinal Anastomosis of Rats

    Directory of Open Access Journals (Sweden)

    Marjan Joudi

    2016-02-01

    Full Text Available Background In this study, given the importance of gastrointestinal anastomosis in surgical procedures, attempts have been made to compare the results of employing magnetic compression anastomosis and magnetic coils in intestinal anastomosis of rats. Materials and Methods This study was an experimental trial on 60 rats which had been randomly divided into two experiment (30 and control (30 groups. First, the rat intestine was cut off from a relatively fixed point and then magnet anastomosis was performed at the both ends of bowel in the control group and manual suture in the experiment group.  Anastomosis was then examined 10 days after the surgery for possible complications with a histological analysis of the indices of tissue repair. Results The mean time required for performing anastomosis of the rat intestine was 735 and 366 seconds for the control and experiment groups, respectively. Also, the laparotomy performed 10 days after the first operation did not show any significant difference between two groups in terms of surgical complications such as infiltration factor of inflammatory cell and fibroblast activity (P>0.05. The microscopic examination indicated that the tissue reaction in the anastomosis site was better in terms of tissue repair of neo-angiogenesis intestine and collagen deposition in the magnet group(P>0.05.   Conclusion Given the shorter duration of the anastomosis by magnets and more favorable histological results reported in the experiment group, as well as the lack of any significant difference in complications of the two techniques, magnetic compressive anastomosis can be used as a new technique for intestinal surgeries and pertaining anastomosis. Although, we recommend that study will be done with large sample size to obtain reliable results.

  8. Role of amygdala MAPK activation on immobility behavior of forced swim rats.

    Science.gov (United States)

    Huang, Tung-Yi; Lin, Chih-Hung

    2006-10-01

    The role of amygdala mitogen-activated protein kinase (MAPK) in rats during a forced swim test was investigated. The variation of amygdala MAPK level was studied in control rats and early-life maternally deprived rats. A forced swim test was carried out to estimate the immobility level. The data showed that the immobility time of rats that received maternal deprivation in early life was longer than that of control rats and Western blot analysis also showed that the amygdala phospho-MAPK level in maternally deprived rats was almost two times higher than in control rats. Intra-amygdala infusion of PD098059 or U0126, MEK inhibitors, suppressed immobility behavior during the forced swim test in both rats. Western blot analysis also showed that the amygdala MAPK activities in both rats infused with MEK inhibitors were also suppressed in parallel with expression of immobility behavior. The suppressed MAPK activities as well as the restoration of immobility time returned to the original level 48 h later. These results suggest that amygdala MAPK activation might play a role in the regulation of immobility behavior in rats during the forced swim test. Moreover, it could provide a hint that amygdala MAPK activation might be involved in the formation of depression-like behavior.

  9. The Role of Dual-Trained Conventional/Complementary Physicians as Mediators of Integration in Primary Care

    Directory of Open Access Journals (Sweden)

    Eran Ben-Arye

    2010-01-01

    Full Text Available A growing number of physicians study complementary and alternative medicine (CAM. Limited data are available on perspectives of physicians with dual training in conventional medicine and CAM, on issues of communication and collaboration with CAM practitioners (CAMPs. Questionnaires were administered to primary care physicians employed in the largest health maintenance organization (HMO in Israel and to MD and non-MD CAM practitioners employed by a CAM-related agency of the same HMO. Data for statistical analysis were available from 333 primary care physicians (PCPs and 241 CAM practitioners. Thirty-one of the 241 CAMPs were dual-trained physicians employed in a CAM-related agency as practitioners and/or triage-consultants. Dual trained physicians and CAMPs shared similar attitudes and supported, more so than PCPs, collaborative physician–CAM practitioner teamwork in clinical practice, medical education and research. Nevertheless, dual trained physicians supported a physician-dominant teamwork model (similar to the PCPs’ approach in contrast to non-MD CAM practitioners who mainly supported a co-directed teamwork model. Compared to PCPs and non-MD CAM practitioners, dual trained physicians supported significantly more a medical/referral letter as the preferred means of doctor–CAM practitioner communication. Dual trained physicians have a unique outlook toward CAM integration and physician–practitioner collaboration, compared to non-MD CAM practitioners and PCPs. More studies are warranted to explore the role of dual trained physicians as mediators of integration.

  10. Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

    Science.gov (United States)

    Fernández-Repollet, E; Martínez-Maldonado, M; Opava-Stitzer, S

    1980-08-01

    1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic

  11. Role of stanniocalcin1 in brain injury of coal-burning-borne fluorosis rats

    Institute of Scientific and Technical Information of China (English)

    陈旭义

    2013-01-01

    Objective To observe the change of stanniocalcin 1(STC1) and calcium content in brain of coal-burning-borne fluorosis rats,and to explore the role of STC1 in brain injury of coal-burning-borne fluorosis.Methods Twenty four male SD rats were randomly divided into control,low,medium,

  12. Role of orexin receptors in the nucleus accumbens in dopamine-dependent turning behaviour of rats.

    NARCIS (Netherlands)

    Kotani, A.; Ikeda, H.; Koshikawa, N.; Cools, A.R.

    2008-01-01

    The role of orexin receptors in the nucleus accumbens shell in rat turning behaviour of rats was studied. Unilateral injection of neither the orexin 1 and 2 receptor agonist orexin A (2 microg) nor the orexin 1 receptor antagonist SB 334867 (20 ng) into the nucleus accumbens shell elicited turning b

  13. Effect of Intra CA1 and Intraperitoneal Administration of Opioid Receptor Modulating Agents on The Anxiolytic Properties of Nano and Conventional ZnO in Male Rats

    Directory of Open Access Journals (Sweden)

    Mozhgan Torabi

    2014-06-01

    Full Text Available Objective: Nano components are today’s new wonder material. However, the safety or toxicity of these components in humans is not yet clear. In a previous study we indicated that nano ZnO (nZnO has a stronger anxiolytic effect compared to the conventional ZnO (cZnO. The present study was designed to evaluate the intraperitoneal administration of an opioidergic receptor agonist and antagonist of as well as the intra CA1 administration of an opioidergic receptor antagonist on the anxiolytic properties of nano and conventional ZnO in adult male Wistar rats. Materials and Methods: In this experimental study, rats received drugs via two modes of injection; intraperitoneal (IP. and intra CA1 (intra hippocampus, CA1 area. Firstly, nZnO (5, 10, 20 mg/kg, cZnO (5, 10, 20 mg/kg, morphine 6 mg/kg, and naloxone 1 mg/kg were injected IP and naloxone 1μg/rat was injected intra CA1. Subsequently, morphine and naloxone (IP and intra CA1 were co-injected with the effective dose of nZnO and cZnO. An elevated plus maze was used to evaluate anxiety related behavior and anxiety parameters 30 minutes after the second injection. Results: The results indicated that the anxiolytic effects of nZnO 5 mg/kg and cZnO 10 mg/kg were equal. When injected intraperitoneally, naloxone increased anxiety but did not inhibit the anxiolytic effect of nZnO and cZnO. The anxiolytic effects of morphine potentiated the anxiolytic effects of ZnO, particularly nZno. When introduced via intra CA1 injection naloxone alone had no effect on anxiety behaviors and did not inhibit the anxiolytic effect of nZnO. Conclusion: It seems that the opioidergic system activity involved in the anxiolytic effect of nano and conventional ZnO may operate through shared and unshared pathways.

  14. Biological responses in rats exposed to mainstream smoke from a heated cigarette compared to a conventional reference cigarette.

    Science.gov (United States)

    Fujimoto, Hitoshi; Tsuji, Hiroyuki; Okubo, Chigusa; Fukuda, Ichiro; Nishino, Tomoki; Lee, K Monica; Renne, Roger; Yoshimura, Hiroyuki

    2015-03-01

    The heated cigarette (HC) generates mainstream smoke by vaporizing the components of the tobacco rod using a carbon heat source at the cigarette tip. Mainstream smoke of HC contains markedly less chemical constituents compared to combusted cigarettes. Mainstream smoke from HC was generated under Health Canada Intense regimen and its biological effects were compared to those of Reference (3R4F) cigarettes, using nose-only 5-week and 13-week inhalation studies. In the 13-week study, SD rats were necropsied following exposure to mainstream smoke from each cigarette at 200, 600 or 1000 µg wet total particulate matter/L for 1 h/day, 7 days/week or following a 13-week recovery period. Histopathological changes in the respiratory tract were significantly lesser in HC groups; e.g. respiratory epithelial hyperplasia in the nasal cavity and accumulation of pigmented macrophages in alveoli. After a 13-week recovery, the lesions were completely or partially regressed, except for accumulation of pigmented macrophages in alveoli, in both HC and 3R4F groups. In the 5-week study, SD rats were necropsied following exposure to mainstream smoke of either cigarette at 600 or 1000 µg/L for 1 h, two times/day (with 30 min interval), 7 days/week or following a 4-week recovery period. Bronchoalveolar lavage fluid (BALF) analysis of neutrophil percentages and enzyme levels like γ-GT, ALP and LDH indicated that pulmonary inflammation was significantly less in HC groups compared to 3R4F groups. In conclusion, HC demonstrated significantly lower biological effects compared to 3R4F, based on the BALF parameters and histopathology.

  15. Cryopreservation of Rat Bone Marrow Derived Mesenchymal Stem Cells by Two Conventional and Open-pulled Straw Vitrification Methods

    Directory of Open Access Journals (Sweden)

    Mohammad Hadi Bahadori

    2009-01-01

    Full Text Available Objective: Mesenchymal stem cells (MSCs are obtained from a variety of sources, mainlythe bone marrow. These cells have a great potential for clinical research, however they cannotstay alive for long periods in culture. The aim of this study is to determine whether vitrificationcan be a useful freezing method for the storage of MSCs.Materials and Methods: Mesenchymal stem cells were isolated from rat bone marrow basedon their capacity to adhere to plastic culture surfaces. MSCs were cryopreserved using boththe vitrification method and open-pulled straw (OPS vitrification and stored in liquid nitrogenwith ethylene glycol ficoll (EFS as a cryoprotectant for two months. The morphology andviability of thawed MSCs were evaluated by trypan blue staining. Furthermore, pre and postcryopreserved MSCs were induced to osteocyte and adipocyte with corresponding osteogenicand adipogenic medium.Results: After thawing, the viability rates were 81.33% ± 6.83 for the vitrification method and80.83% ± 6.4 for OPS vitrification, while the values in the pre-vitrification control group were88.16% ± 6.3 (Mean ± SD, n = 6. Post-cryopreserved cells from both the vitrification methodand OPS vitrification also had a similar cellular morphology and colony-formation that wasindistinguishable from non-vitrified fresh MSCs. In addition, the resuscitated cells cultured ininduction medium showed osteogenesis. Mineral production and deposition was detectableby alizarine red S staining. Moreover, by applying an adipogenic differentiation condition,both pre and post cryopreserved cells differentiated into adipocyte and lipid vacuole accumulationthat was stained by oil red O.Conclusion: Vitrification is a reliable and effective method for the cryopreservation of MSCs.

  16. Le Role des ONG dans la Mise en Application de la Convention des Droit de l'Enfant (The Role of Non Governmental Organizations in the Implementation of the Convention on the Rights of the Child).

    Science.gov (United States)

    Goutard, M.

    1992-01-01

    Examines cooperative efforts among nongovernmental organizations (NGOs) in France to implement the United Nation's Convention on the Rights of the Child. Describes collaborative efforts between NGO committees and government authorities, highlighting government experts' recommendations for changes in four areas of French law to conform to…

  17. Altered placental development in undernourished rats: role of maternal glucocorticoids

    Directory of Open Access Journals (Sweden)

    Chen Chun-Hung

    2011-08-01

    Full Text Available Abstract Maternal undernutrition (MUN during pregnancy may lead to fetal intrauterine growth restriction (IUGR, which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1, 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1 predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC to corticosterone, although can sometimes drive the opposing (inactivating reaction, and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents in control and MUN rats at embryonic day 20 (E20. Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3 and amino acids (SLC38A1, 2, and 4. Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC

  18. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...... of rat MIP-1 alpha. The resulting product shared 92% and 90% homology with the known murine sequence at the cDNA level and protein level, respectively. Recombinant rat MIP-1 alpha exhibited dose-dependent chemotactic activity for both rat and human monocytes and neutrophils, which could be blocked...... by anti-murine MIP-1 alpha Ab. Rat MIP-1 alpha mRNA and protein expression were determined as a function of time in both injury models. A time-dependent increase in MIP-1 alpha mRNA in lung extracts was observed in both models. In the LPS model, MIP-1 alpha protein could also be detected...

  19. The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    匡洪宇; 邹伟; 刘丹; 史榕荇; 程丽华; 殷慧清; 刘晓民

    2003-01-01

    Objective To evaluate the potential role of insulin-like growth factor-1 receptor mRNA(IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.Methods A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.Results Weak expression of IGF-IR mRNA(5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P<0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.Conclusion Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

  20. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

    Directory of Open Access Journals (Sweden)

    V. Bertone

    2011-02-01

    Full Text Available Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT. Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS. However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20 that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1, frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but

  1. Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib

    Institute of Scientific and Technical Information of China (English)

    Hai-yan XU; Zhi-yong XIE; Peng ZHANG; Jin SUN; Feng-ming CHU; Zong-ru GUO; Da-fang ZHONG

    2006-01-01

    Aim: To investigate the in vitro metabolism of imrecoxib in rat liver microsomes and to identify the cytochrome P450 (CYP) forms involved in its metabolism. Methods: Liver microsomes of Wistar rats were prepared using an ultracentrifuge. The in vitro metabolism of imrecoxib was studied by incubation with rat liver microsomes. To characterize the CYP forms involved in the 4'-methyl hydroxylation of imrecoxib, the effects of typical CYP inducers (such as dexamethasone, isoniazid and (3-naphthoflavone) and of CYP inhibitors (such as ketoconazole, quinine, a-naphthoflavone, methylpyrazole, and cimetidine) on the formation rate of 4'-hydroxymethyl imrecoxib were investigated. Results: Imrecoxib wasmetabolized to 3 metabolites by rat liver microsomes: 4'-hydroxymethyl imrecoxib (M4), 4'-hydroxymethyl-5-hydoxyl imrecoxib (M3), and 4'-hydroxymethyl-5-carbonyl imrecoxib (M5). Over the imrecoxib concentration range studied (5-600 umol/L), the rate of 4'-methyl hydroxylation conformed to monophasic Michaelis-Menten kinetics. Dexamethasone significantly induced the formation of M4. Ketoconazole markedly lowered the metabolic rate of imrecoxib in a concentration-dependent manner. Moreover, a significant inhibitory effect of quinine on the formation of M4 was observed in microsomes obtained from control rats, isoniazid-induced rats, and (3-naphthoflavone-induced rats. In contrast, α-naphthoflavone, cimetidine, and methylpyrazole had no inhibitory effects on this metabolic pathway. Conclusion: Imrecoxib is metabolized via 4'-methyl hydroxylation in rat liver microsomes. The reaction is mainly catalyzed by CYP 3A. CYP 2D also played a role in control rats, in isoniazid-induced rats and in β-naphthoflavone-induced rats.

  2. 城市会展业发展中的政府角色探析%Government's Role in Urban Convention and the Development of Exposition Industry

    Institute of Scientific and Technical Information of China (English)

    赵伯艳

    2011-01-01

    Urban convention and exposition industry will promote urban economic development and improve the fame of city. Municipal government plays an important role in pushing forward the development of convention and exposition industry, and undertakes important responsibility at the same time. At present, there exist some problems in municipal government' s management mode of convention and exposition industry such as indistinetion between government' s role and enterprise' s role, poor coordination, weak supervision and lack of service. In view of the existing problems, munici- pal government should orientate its role accurately and play the following roles such as guider of development orientation, development planner, architect of development environment, brand supporter, coordinator, server and regulator, and trainer of professional talents in local convention and exposition industry.%发展良好的城市会展业是带动城市经济发展的新的增长点,有助于提高城市的知名度。城市政府在会展业的推进发展中起着重要的作用,同时也承担着重要的责任。针对当前城市政府在会展业发展中存在的政企不分、协调性差、监管乏力以及服务缺失等问题,政府应准确定位其自身角色,扮演好本地会展业发展的定位者、规划者、环境塑造者、品牌建设扶持者、协调者、服务者、监管的规制者和专业人才培育者等角色。

  3. Effect of crop protection and fertilization regimes used in organic and conventional production systems on feed composition and physiological parameters in rats.

    Science.gov (United States)

    Srednicka-Tober, Dominika; Barański, Marcin; Gromadzka-Ostrowska, Joanna; Skwarło-Sońta, Krystyna; Rembiałkowska, Ewa; Hajslova, Jana; Schulzova, Vera; Cakmak, Ismail; Öztürk, Levent; Królikowski, Tomasz; Wiśniewska, Katarzyna; Hallmann, Ewelina; Baca, Elżbieta; Eyre, Mick; Steinshamn, Håvard; Jordon, Teresa; Leifert, Carlo

    2013-02-01

    Very little is known about the effects of an organic or conventional diet on animal physiology and health. Here, we report the effect of contrasting crop protection (with or without chemosynthetic pesticides) and fertilization (manure or mineral fertilizers) regimes on feed composition and growth and the physiological parameters of rats. The use of manure instead of mineral fertilizers in feed production resulted in lower concentrations of protein (18.8 vs 20.6%) and cadmium (3.33 vs 4.92 μg/100 g) but higher concentrations of polyphenols (1.46 vs 0.89 g/100 g) in feeds and higher body protein (22.0 vs 21.5%), body ash (3.59 vs 3.51%), white blood cell count (10.86 vs 8.19 × 10³/mm³), plasma glucose (7.23 vs 6.22 mmol/L), leptin (3.56 vs 2.78 ng/mL), insulin-like growth factor 1 (1.87 vs 1.28 μg/mL), corticosterone (247 vs 209 ng/mL), and spontaneous lymphocyte proliferation (11.14 vs 5.03 × 10³ cpm) but lower plasma testosterone (1.07 vs 1.97 ng/mL) and mitogen stimulated proliferation of lymphocytes (182 vs 278 × 10³ cpm) in rats. There were no main effects of crop protection, but a range of significant interactions between fertilization and crop protection occurred.

  4. Urine from stressed rats increases immobility in receptor rats forced to swim: role of 2-heptanone.

    Science.gov (United States)

    Gutiérrez-García, Ana G; Contreras, Carlos M; Mendoza-López, M Remedios; García-Barradas, Oscar; Cruz-Sánchez, J Samuel

    2007-05-16

    The present study was aimed to determine whether the urine from donor rats, which were physically stressed (UD-PS) by unavoidable electric footshocks, produces despair in receptor partner rats (RP) in the long-term. For each trial, an RP rat was placed during 10 min once per day for 21 days in a small non-movement-restricting cage impregnated with the urine collected from a UD-PS rat. Control rats, free of stimulation, maintained their locomotion and immobility scores at basal values throughout the 21-day test. After 21 days of stressing experience [F(2,90)=15.22, Pimmobility [F(2,90)=8.83, Pswim test (RP, r=0.886, P<0.05; UD-PS, r=0.962, P<0.001) compared with the control group (r=-0.307, NS). We conclude that the RP became similarly despaired as the UD-PS group through the action of 2-heptanone, a ketonic compound identified in UD-PS urine by HS-GC/MS techniques. This ketone was found to be increased [F(2,15)=3.50, P<0.05] from the 1st day of unavoidable electric footshocks, and to induce despair, an effect reverted [F(2,21)=16.5, P<0.0001] by imipramine (5.0 mg/kg) in another group of rats.

  5. Role of the lung in the progression of multiple organ dysfunction syndrome in ageing rat model

    Institute of Scientific and Technical Information of China (English)

    WANG Xue-ping; ZHU Qing-lei; XUE Qiao; LI Yang; QIAN Xiao-shun; WANG Zhong-liang; WANG Shi-wen

    2012-01-01

    hours,lagging behind that in the lung.Conclusion Lung is the first and most seriously injured organ in rat model of MODSE and it may play an “initiating” role in the development of MODSE.

  6. Functional imaging of infection: conventional nuclear medicine agents and the expanding role of {sup 18-}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Parisi, Marguerite T. [Seattle Children' s Hospital, Department of Radiology R-5417, Seattle, WA (United States)

    2011-07-15

    A growing body of literature suggests that 18-fluorine fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET), particularly when combined with CT, is a useful tool for the detection of infectious and inflammatory disease processes. This article will briefly review the data to date on the use of FDG PET in diagnosing musculoskeletal infections and fever of unknown origin, comparing it to conventional scintigraphic techniques in both adults and, when available, in children. (orig.)

  7. Role of the heme oxygenases in abnormalities of the mesenteric circulation in cirrhotic rats.

    Science.gov (United States)

    Sacerdoti, David; Abraham, Nader G; Oyekan, Adebayo O; Yang, Liming; Gatta, Angelo; McGiff, John C

    2004-02-01

    Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has biological actions similar to those of nitric oxide (NO). The role of CO in decreasing vascular responses to constrictor agents produced by experimental cirrhosis induced by carbon tetrachloride was evaluated before and after inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1 (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE were successively augmented by stepwise inhibition of CO and NO production, suggesting a complementary role for these gases in the regulation of reactivity of the SMV. Expression of constitutive but not of inducible HO (HO-1) was increased in the SMV of cirrhotic rats as was HO activity. Administration of adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated reduction in both perfusion pressure and vasoconstrictor responses to PE in the SMV. We propose that HO is an essential component in mechanisms that modulate reactivity of the mesenteric circulation in experimental hepatic cirrhosis in rats.

  8. The role of TNF-alpha in amygdala kindled rats.

    Science.gov (United States)

    Shandra, A A; Godlevsky, L S; Vastyanov, R S; Oleinik, A A; Konovalenko, V L; Rapoport, E N; Korobka, N N

    2002-02-01

    In the present study, the interaction between epileptogenesis and the immune system were studied in a kindling model. First, the effects of a single administration of TNF-alpha (5.0 microg/kg, i.p.) on seizure and EEG activity were investigated in amygdala-kindled rats. TNF-alpha treated rats showed more prolonged epileptiformic discharges than control rats. TNF-alpha also induced a decrease in the power of delta band and an increase in theta and alpha activity. In addition, a marked increase in the power of beta and gamma band was observed. The EEG changes were most numerous in the frontal cortex and amygdala. All effects were registered 24 h after TNF-alpha administration. Finally, electrical stimulation enhanced the level of TNF-alpha in blood serum from 1.9 +/- 1.5 to 12.7 +/- 3.8 pg/ml and in brain tissue 56.8 +/- 6.0 to 109.2 +/- 6.0 pg/mg, as was determined via the ELISA method. It can be concluded that there is a mutual facilitative interaction of both epileptogenic and cytokine-derived mechanisms on this type of seizure. The changes in the power spectrum of the EEG after TNF-alpha might contribute to intensify thalamic-derived facilitation of epileptic discharge in cortical structures.

  9. The kidneys play a central role in the clearance of rhGH in rats.

    Science.gov (United States)

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads; Fels, Johannes Josef; Lykkesfeldt, Jens; Agersø, Henrik

    2016-04-30

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290 ml/h/kg. This was reduced to 185 ml/h/kg by anesthesia and further reduced to 18 ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.

  10. Electrical energy generation in Europe the current and future role of conventional energy sources in the regional generation of electricity

    CERN Document Server

    Morales Pedraza, Jorge

    2014-01-01

    Maximizing reader insights into the current use of conventional energy sources (such as fossil fuels) in the generation of electricity in the European region, this book addresses several key issues including: potential ways European countries could expand their energy sector in the coming years; the impact on the climate, the level of energy reserves, different efficiency measures that could be adopted to reduce the consumption of fossil fuels in the generation of electricity, and current and future energy production and consumption trends, amongst other topics.   Covering both how the use

  11. Research on the Role of Rat TPP-Ⅰ in Neuromedin B Degradation

    Institute of Scientific and Technical Information of China (English)

    DU Pei-ge; QIU Fang-ping; AN Li-ping; WANG Yan; LU Gang

    2005-01-01

    TPP-Ⅰ(tripeptidyl peptidase-Ⅰ) protein turnover was studied by observing the role of rat TPP-Ⅰ in neuromedin B(NMB) and other neuropeptides degradations in some physiological situations. The mixtures of rat TPP-Ⅰ with each of NMB, other neuropeptides and Ala-Ala-Phe-MCA were made respectively under the same conditions. The reaction was observed at different timeand monitored by means of high performance liquid chromatography(HPLC) and time-of-flight mass spectrometry(TOF-MS) in vitro. NMB was broken down at the same degree as Ala-Ala-Phe-MCA by rat TPP-Ⅰ and Gly-Asn-Leu was released within 16 h, but other neuropeptides were not digested within 24 h. TPP-Ⅰ is the predominant proteolytic enzyme responsible for the intracellular degradation of neuromedin B. NMB has recently been found to be a good natural substrate for rat lysosomal TPP-Ⅰ.

  12. Diving response in rats: role of the subthalamic vasodilator area.

    Directory of Open Access Journals (Sweden)

    Eugene Golanov

    2016-09-01

    Full Text Available Diving response is a powerful integrative response targeted toward survival of the hypoxic/anoxic conditions. Being present in all animals and humans it allows to survive adverse conditions like diving. Earlier we discovered that forehead stimulation affords neuroprotective effect decreasing infarction volume triggered by permanent occlusion of the middle cerebral artery in rats. We hypothesized that cold stimulation of the forehead induces diving response in rats, which, in turn, exerts neuroprotection. We compared autonomic (AP, HR, CBF and EEG responses to the known diving response-triggering stimulus, ammonia stimulation of the nasal mucosa, cold stimulation of the forehead, and cold stimulation of the glabrous skin of the tail base in anesthetized rats. Responses in AP, HR, CBF and EEG to cold stimulation of the forehead and ammonia vapors instillation into the nasal cavity were comparable and differed significantly from responses to the cold stimulation of the tail base. Excitotoxic lesion of the subthalamic vasodilator area, which is known to participate in CBF regulation and to afford neuroprotection upon excitation, failed to affect autonomic components of the diving response evoked by forehead cold stimulation or nasal mucosa ammonia stimulation. We conclude that cold stimulation of the forehead triggers physiological response comparable to the response evoked by ammonia vapor instillation into the nasal cavity, which considered as stimulus triggering protective diving response. These observations may explain the neuroprotective effect of the forehead stimulation. Data demonstrate that subthalamic vasodilator area does not directly participate in the autonomic adjustments accompanying diving response, however, it is involved in diving-evoked modulation of EEG. We suggest that forehead stimulation can be employed as a stimulus capable of triggering oxygen-conserving diving response and can be used for neuroprotective therapy.

  13. Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

    LENUS (Irish Health Repository)

    Abdel Aziz, Mohamed T

    2011-05-05

    Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

  14. Hydrogen sulfide alleviates uranium-induced acute hepatotoxicity in rats: Role of antioxidant and antiapoptotic signaling.

    Science.gov (United States)

    Yuan, Yan; Zheng, Jifang; Zhao, Tingting; Tang, Xiaoqing; Hu, Nan

    2017-02-01

    As an endogenous gaseous mediator, H2 S exerts antioxidative, antiapoptotic, and cytoprotective effects in livers. This study was designed to investigate the protective role of H2 S against uranium-induced hepatotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2 S production was determined in livers. The levels of endogenous H2 S and H2 S-producing enzymes (CBS and CSE) were measured in liver homogenates from uranium -intoxicated rats. In rats injected intraperitoneally (i.p.) with uranyl acetate or NaHS (an H2 S donor) alone or in combination, we examined biochemical parameters to assess liver function, revealed hepatic histopathological alteration, investigated oxidative stress markers, and explored apoptotic signaling in liver homogenates. The results suggest that uranium-intoxication in rats decreased CBS and CSE protein expression, H2 S synthesis capacity, and endogenous H2 S generation. NaHS administration in uranium-intoxicated rats produced amelioration in liver biochemical indices and histopathological effects, decreased MDA content, and increased GSH level and antioxidative enzymes activities like SOD, CAT, GPx, and GST. NaHS administration in uranium-intoxicated rats attenuated uranium-activated phosphorylation state of JNK. NaHS treatment in uranium-intoxicated rats increased antiapoptotic Bcl-2 but decreased pro-apoptotic Bax, resulting in the rise of Bcl-2/Bax ratio. NaHS treatment in uranium-intoxicated rats reduced the apoptosis mediator caspase-3 and cytochrome c release and elevated ATP contents. Taken together, these data implicate that H2 S can afford protection to rat livers against uranium-induced adverse effects mediated by up-regulation of antioxidant and antiapoptotic signaling. The anti-apoptotic property of H2 S may be involved, at least in part, in inhibiting JNK signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 581-593, 2017.

  15. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    Science.gov (United States)

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion.

  16. Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

    Directory of Open Access Journals (Sweden)

    Sabry Dina

    2011-05-01

    Full Text Available Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs in an experimental hepatocellular carcinoma (HCC model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA and CCl4, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA, cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell

  17. Role of group 3 innate lymphoid cells during experimental otitis media in a rat model.

    Science.gov (United States)

    Cho, Chang Gun; Gong, Sung Ho; Kim, Hee-Bok; Song, Jae-Jun; Park, Joo Hyun; Lim, Yun-Sung; Park, Seok-Won

    2016-09-01

    The objective of this study was to evaluate the role of group 3 innate lymphoid cells (ILC3) in the middle ear (ME) mucosal response to bacterial infection in a rat model. To confirm the role of ILC3 in bacterially induced otitis media (OM), the serum concentrations of IL-17 and IL-22 were determined by ELISA, and the tissue expression of IL-17 and IL-22 in infected ME mucosa was assessed by immunohistochemical staining. Immunohistochemical staining of specific cell surface markers was also assessed to confirm the origin of the cells expressing IL-17 and IL-22. Twenty Sprague-Dawley rats were used in the surgically-induced animal model of OM. OM was induced by inoculation of non-typeable Haemophilus influenzae into the ME cavity of the rats. The rats were divided into four experimental groups: three infected groups and one control group. Infected groups were subdivided into sets of 5 rats, one for each of the three time points (1, 4 and 7 days post-inoculation). For determination of rat IL-17 and IL-22 levels in infected rats and control rats, infected or control ME mucosa sections were analyzed by immunohistochemistry with specific antibodies directed against IL-17 and IL-22. Immunohistochemical staining for CD3, RORγt, and NKp46 were also conducted on the samples to confirm the origin of cells expressing IL-17 and IL-22. IL-17 and IL-22 serum concentrations were significantly increased in the infected rats compared to control rats. Immunohistochemical staining revealed increased IL-17 and IL-22 expressions in all infected ME mucosae from the first day after inoculation. In addition, the results of tissue staining for the specific surface markers were negative for CD3 and NKp46, but were highly positive for RORγt. IL-17 and IL-22 revealed their association with the bacterially induced proliferative and hyperplastic responses of ME mucosa, which are characteristic features in pathogenesis of OM. Surface marker examination showed that the source cells for IL-17

  18. Role of cholecystokinin in dietary fat-promoted azaserine-induced pancreatic carcinogenesis in rats

    NARCIS (Netherlands)

    Appel, M.J.; Meijers, M.; Garderen-Hoetmer, A. van; Lamers, C.B.H.W.; Rovati, L.C.; Sprij-Mooij, D.; Jansen, J.B.M.J.; Woutersen, R.A.

    1992-01-01

    The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturat

  19. THE ROLE OF SECRETORY GRANULES IN RADIATION-INDUCED DYSFUNCTION OF RAT SALIVARY-GLANDS

    NARCIS (Netherlands)

    PETER, B; VANWAARDE, MAWH; VISSINK, A; SGRAVENMADE, EJ; KONINGS, AWT

    To investigate the possible role of secretory granules in radiation-induced salivary gland dysfunction, rats were pretreated with isoproterenol (5 mg/kg intraperitoneally) to degranulate salivary gland acini, At maximal depletion, salivary glands were locally irradiated with a single dose of 15 Gy

  20. Protective Role of Aerobic Exercise Against Cisplatin-Induced Nephrotoxicity in Rats

    OpenAIRE

    Zeynali; Nematbakhsh; Mojtahedi; Poorshahnazari; Talebi; Pezeshki; Mazaheri; Moslemi

    2015-01-01

    Background Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is considered as its major side effect. Aerobic exercise is well known as an approach to reduce the side effects of many drugs. Objectives This study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity. Materials and Methods Thirty male Wistar rats were randomly divid...

  1. THE ROLE OF SECRETORY GRANULES IN RADIATION-INDUCED DYSFUNCTION OF RAT SALIVARY-GLANDS

    NARCIS (Netherlands)

    PETER, B; VANWAARDE, MAWH; VISSINK, A; SGRAVENMADE, EJ; KONINGS, AWT

    1995-01-01

    To investigate the possible role of secretory granules in radiation-induced salivary gland dysfunction, rats were pretreated with isoproterenol (5 mg/kg intraperitoneally) to degranulate salivary gland acini, At maximal depletion, salivary glands were locally irradiated with a single dose of 15 Gy o

  2. Role of L-type calcium-channel modulation in nonconvulsive epilepsy in rats

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Ates, N.; Coenen, A.M.L.

    1995-01-01

    Old male Wistar rats spontaneously showing hundreds of spike-wave discharges daily were used to investigate the role of calcium ions in nonconvulsive epilepsy. The effects of the L-type calcium channel blocker nimodipine and the L-type channel opener BAY K 8644 on number and duration of these spike-

  3. Conducted vasoconstriction in rat mesenteric arterioles: role for dihydropyridine-insensitive Ca(2+) channels

    DEFF Research Database (Denmark)

    Gustafsson, F; Andreasen, D; Salomonsson, Max;

    2001-01-01

    The aim of this study was to evaluate the role of voltage-operated Ca(2+) channels in the initiation and conduction of vasoconstrictor responses to local micropipette electrical stimulation of rat mesenteric arterioles (28 +/- 1 microm, n = 79) in vivo. Local and conducted (600 microm upstream fr...

  4. GEMSP exerts a myelin-protecting role in the rat optic nerve.

    Science.gov (United States)

    Mangas, Arturo; Vecino, Elena; David Rodríguez, F; Geffard, Michel; Coveñas, Rafael

    2013-11-01

    Chronic experimental autoimmune encephalomyelitis (EAE) was induced in rats to evaluate the potential protective effect of GEMSP, a mixture made up of fatty acids (FA), vitamins, and amino acids or their derivatives, linked to Poly-L-Lysine, on the myelin sheath of the optic nerve. To evaluate the effects of GEMSP on the optic nerve, animals were divided into three experimental groups: (1) EAE rats treated with GEMSP; (2) EAE rats treated with 0.9% NaCl; and (3) control, non-EAE rats. Using electron microscopy, we investigated the possibility that this new drug candidate has a myelin-protective role. A marginally significant reduction in the thickness of the myelin around optic nerve medium-size axons (diameter between 0.8-1.3 μm) was found in EAE rats. Treatment of EAE rats with GEMSP ameliorated myelin damage. Significantly increased myelin thickness was found when animals in groups 2 and 3 were compared. However, the number of myelinated axons studied was not altered in groups 1 or 2 when compared to controls. Our results suggest that in a model of demyelination, GEMSP protects and enhances the formation of the myelin sheath of the optic nerve and therefore could be a potential drug candidate to reduce optic nerve pathogenesis in multiple sclerosis (MS).

  5. Protective role of a novel human erythrocyte-derived depressing factor on blood vessels in rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The protective role of a human erythrocyte-derived depressing factor (EDDF) on blood vessels was evaluated. The experiments were carried out on 25male Wistar rats aged 6-8 weeks, which were divided into control (n = 8), calcium overload (n = 8) and NG-L-nitro-arginine hypertensive model groups (L-NNA,n = 9), respectively. The isolated vascular ring perfusion assay, two-photon laser scanning fluorescence microscopy (TPM) and transmitted electron microscope were used to examine the effect of EDDF on vascular function and ultrastructure. Results showed that the contractile response of calcium overload rats and L-NNA rats to phenylephrine (PE) was significantly enhanced compared with that of the control (P < 0.05), and EDDF (10-3 g @mL-1) remarkably decreased the vascular contractile response of control's and calcium overload rats (P < 0.05),while EDDF had no effect on that of L-NNA rats. EDDF also alleviated the ultrastructural lesion of aorta VSMC in calcium overload rats by easing the abnormal in the nucleus, mitochondrion and other organell. It is concluded that EDDF could efficiently protect blood vessels against injury by influencing Ca2+ transport and ameliorating the lesion of VSMC, and further supported the hypothesis that the NO-cGMP pathway might contribute to the vasodilation and partially antihypertensive mechanism of EDDF.``

  6. Social transmission of fear in rats: the role of 22-kHz ultrasonic distress vocalization.

    Directory of Open Access Journals (Sweden)

    Eun Joo Kim

    Full Text Available BACKGROUND: Social alarm calls alert animals to potential danger and thereby promote group survival. Adult laboratory rats in distress emit 22-kHz ultrasonic vocalization (USV calls, but the question of whether these USV calls directly elicit defensive behavior in conspecifics is unresolved. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated, in pair-housed male rats, whether and how the conditioned fear-induced 22-kHz USVs emitted by the 'sender' animal affect the behavior of its partner, the 'receiver' animal, when both are placed together in a novel chamber. The sender rats' conditioned fear responses evoked significant freezing (an overt evidence of fear in receiver rats that had previously experienced an aversive event but not in naïve receiver rats. Permanent lesions and reversible inactivations of the medial geniculate nucleus (MGN of the thalamus effectively blocked the receivers' freeezing response to the senders' conditioned fear responses, and this occurred in absence of lesions/inactivations impeding the receiver animals' ability to freeze and emit 22-kHz USVs to the aversive event per se. CONCLUSIONS/SIGNIFICANCE: These results--that prior experience of fear and intact auditory system are required for receiver rats to respond to their conspecifics' conditioned fear responses--indicate that the 22-kHz USV is the main factor for social transmission of fear and that learning plays a crucial role in the development of social signaling of danger by USVs.

  7. Dual role of GABA in the neonatal rat hippocampus.

    Science.gov (United States)

    Khalilov, I; Dzhala, V; Ben-Ari, Y; Khazipov, R

    1999-11-01

    The effects of modulators of GABA-A receptors on neuronal network activity were studied in the neonatal (postnatal days 0-5) rat hippocampus in vitro. Under control conditions, the physiological pattern of activity of the neonatal hippocampal network was characterized by spontaneous network-driven giant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacine (1-2 microM) and the allosteric modulator diazepam (2 microM) induced biphasic responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GABA-A receptor antagonists bicuculline (10 microM) and picrotoxin (100 microM) blocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interictal- and ictal-like activities in the hippocampal slices and the intact hippocampus. These data suggest that at early postnatal ages GABA can exert a dual - both excitatory and inhibitory - action on the network activity.

  8. Role of the amygdala in the hippocampal kindling effect of rats.

    Science.gov (United States)

    Araki, H; Aihara, H; Watanabe, S; Yamamoto, T; Ueki, S

    1985-02-01

    In the present experiment, the role of the amygdala in the formation of the hippocampal kindling effect was investigated in rats with chronic electrode implants. The number of trials required for the establishment of hippocampal kindling was significantly shortened by either ipsilateral or bilateral amygdaloid lesions. The high amplitude spike waves in the frontal cortex and reticular formation appeared earlier in the amygdaloid lesioned rats than in the sham lesioned rats. It is suggested that the amygdala has an inhibitory effect on the development of the hippocampal kindling effect. On the other hand, either the ipsilateral or bilateral amygdaloid lesions after the establishment of hippocampal kindling inhibited the induction of generalized convulsion by hippocampal stimulation. Three and 8 repeated daily stimulations were needed to reestablish the hippocampal kindling effect after the ipsilateral and bilateral amygdaloid lesions, respectively. These results do not coincide with the above-mentioned results indicating that the amygdala has an inhibitory role in the formation of hippocampal kindling. It is suggested that the neuronal circuits involved in the formation of hippocampal kindling in the amygdaloid lesioned rats are different from those in the intact rats.

  9. THE ROLE OF SATELLITE CELLS IN CRUSH INJURY OF RAT SKELETON MUSCLE

    Directory of Open Access Journals (Sweden)

    DilekBURUKOĞLU

    2013-02-01

    Full Text Available The crush type of injury in rat skeletal muscle is often used in tissue degeneration and regeneration. After crush injury muscle tissue begins to regenerate. In this process, it is accepted that satellite cells play an important role which are very sensitive to muscle injury. The aim of this microscopic study was to examine role of satellite cells in muscle regeneration in crush injury. This research was done the department of Histology&Embryology in Eskişehir Osmangazi University in 2008. Ethic approval of this study has been received. During the study, the whole essential and ethics conditionshave been done. In the study 36 Spraque-Dawley rats were used. The rats were separated into 5 groups as test and control groups. Crush type of injury has been applied on muscles of right hind extremitiesof testing group rats by applying 3.5 kg of weight for 6 hours. In according to testing periods rats were anaesthetized intraperitoneally with ketamine 30mg/kg + xylazine 10mg/kg and sacrificied 3, 7, 14 and 21-day intervals. After crush injury, increased satellite cells were particularly observed on day 7. Alsosignificant increased of satellite cells and regenerated myofibrils were detected on day 14. However, satellite cells were seen on day-21 were similar to control group. In crush injuries, number of satellitecells were markedly increased and actively involved into regeneration process of the skeleton muscle.

  10. Role of taurine on acid secretion in the rat stomach

    Science.gov (United States)

    2011-01-01

    Background Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. Methods The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. Results We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphat) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p taurine concentrations with cAMP was observed. Conclusions Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach. PMID:21294907

  11. Role of taurine on acid secretion in the rat stomach

    Directory of Open Access Journals (Sweden)

    Ho Jau-Der

    2011-02-01

    Full Text Available Abstract Background Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA. Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. Methods The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. Results We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD, and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphat in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p Conclusions Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

  12. Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

    Science.gov (United States)

    Liu, Xu-Hui; Yang, Yue-Wu; Dai, Hai-Tao; Cai, Song-Wang; Chen, Rui-Han; Ye, Zhi-Qiang

    2015-01-01

    AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway. PMID:26715807

  13. Competing Role of Bioactive Constituents in Moringa oleifera Extract and Conventional Nutrition Feed on the Performance of Cobb 500 Broilers

    Directory of Open Access Journals (Sweden)

    Govindarajan Karthivashan

    2015-01-01

    Full Text Available The influence of Moringa oleifera (MO leaf extract as a dietary supplement on the growth performance and antioxidant parameters was evaluated on broiler meat and the compounds responsible for the corresponding antioxidant activity were identified. 0.5%, 1.0%, and 1.5% w/v of MO leaf aqueous extracts (MOLE were prepared, and nutritional feed supplemented with 0%, 0.5%, 1.0%, and 1.5% w/w of MO leaf meal (MOLM extracts were also prepared and analysed for their in vitro antioxidant potential. Furthermore, the treated broiler groups (control (T1 and treatment (T2, T3, and T4 were evaluated for performance, meat quality, and antioxidant status. The results of this study revealed that, among the broilers fed MOLM, the broilers fed 0.5% w/w MOLM (T2 exhibited enhanced meat quality and antioxidant status (P<0.05. However, the antioxidant activity of the MOLE is greater than that of the MOLM. The LC-MS/MS analysis of MOLM showed high expression of isoflavones and fatty acids from soy and corn source, which antagonistically inhibit the expression of the flavonoids/phenols in the MO leaves thereby masking its antioxidant effects. Thus, altering the soy and corn gradients in conventional nutrition feed with 0.5% w/w MO leaves supplement would provide an efficient and cost-effective feed supplement.

  14. The cytokines IL-21 and GM-CSF have opposing regulatory roles in the apoptosis of conventional dendritic cells.

    Science.gov (United States)

    Wan, Chi-Keung; Oh, Jangsuk; Li, Peng; West, Erin E; Wong, Elizabeth A; Andraski, Allison B; Spolski, Rosanne; Yu, Zu-Xi; He, Jianping; Kelsall, Brian L; Leonard, Warren J

    2013-03-21

    Interleukin-21 (IL-21) has broad actions on T and B cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive α-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon-γ (IFN-γ)-producing CD4+ T cells in Il21r(-/-)Rag2(-/-) mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2(-/-) mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Competing role of bioactive constituents in Moringa oleifera extract and conventional nutrition feed on the performance of Cobb 500 broilers.

    Science.gov (United States)

    Karthivashan, Govindarajan; Arulselvan, Palanisamy; Alimon, Abd Razak; Safinar Ismail, Intan; Fakurazi, Sharida

    2015-01-01

    The influence of Moringa oleifera (MO) leaf extract as a dietary supplement on the growth performance and antioxidant parameters was evaluated on broiler meat and the compounds responsible for the corresponding antioxidant activity were identified. 0.5%, 1.0%, and 1.5% w/v of MO leaf aqueous extracts (MOLE) were prepared, and nutritional feed supplemented with 0%, 0.5%, 1.0%, and 1.5% w/w of MO leaf meal (MOLM) extracts were also prepared and analysed for their in vitro antioxidant potential. Furthermore, the treated broiler groups (control (T1) and treatment (T2, T3, and T4)) were evaluated for performance, meat quality, and antioxidant status. The results of this study revealed that, among the broilers fed MOLM, the broilers fed 0.5% w/w MOLM (T2) exhibited enhanced meat quality and antioxidant status (P < 0.05). However, the antioxidant activity of the MOLE is greater than that of the MOLM. The LC-MS/MS analysis of MOLM showed high expression of isoflavones and fatty acids from soy and corn source, which antagonistically inhibit the expression of the flavonoids/phenols in the MO leaves thereby masking its antioxidant effects. Thus, altering the soy and corn gradients in conventional nutrition feed with 0.5% w/w MO leaves supplement would provide an efficient and cost-effective feed supplement.

  16. Role(s) of Gravitational Loading on the Growth-Related Transformation of Fiber Phenotype in Rat Soleus

    Science.gov (United States)

    Ohira, Yoshinobu; Kawano, Fuminori; Goto, Katsumasa; Terada, Masahiro; Ohira, Takashi; Nakai, Naoya; Higo, Yoko; Yoshioka, Toshitada

    2008-06-01

    Effects of gravitational loading or unloading on the gain of the characteristics in soleus muscle fibers were studied in rats. The tail suspension was performed in newborn rats from the postnatal day 4 to month 3 and the reloading was allowed for 3 months in some rats. Single expression of type I myosin heavy chain (MHC) was observed in ~82% fibers in 3month old controls, but fibers expressing multiple MHC iso-forms were noted in the unloaded rats. Responses of fast or slow MHC protein expression to growth and/or unloading were not directly related to mRNA expression. Although 97% fibers in 3month old controls had a single neuromuscular junction at the central region of fiber, fibers with multiple nerve endplates were seen in the unloaded group. Faster contraction speed and lower maximal tension development, even after normalization with fiber size, were observed in the unloaded pure type I MHC fibers. These parameters generally returned to the age-matched control levels after reloading. It was suggested that antigravity-related tonic activity plays an important role in the gain of single neural innervation and of slow contractile properties and phenotype in soleus muscle fibers, which are not directly related to gene expression.

  17. Nonpreventive Role of Aerobic Exercise Against Cisplatin-induced Nephrotoxicity in Female Rats

    OpenAIRE

    Jalaledin Noroozi; Farzaneh Zeynali; Mehdi Nematbakhsh; Zahra Pezeshki; Ardeshir Talebi

    2015-01-01

    Background: Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is a major concern for CP therapy. CP-induced nephrotoxicity is gender-dependent, and the effect of aerobic exercise in females has not been reported yet while it has a beneficial effect in males. Hence, this study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity in female rats. Methods: Twenty-eight adult female rats were divided into four groups. Groups I and II had ae...

  18. Role of putative neurotransmitters in the central gastric antisecretory effect of prostaglandin E2 in rats.

    OpenAIRE

    Puurunen, J.

    1985-01-01

    The role of putative neurotransmitters of the central nervous system in the central gastric antisecretory effect of prostaglandin E2 (PGE2) was investigated in pylorus-ligated rats. Pretreatment of the rats with an intracerebroventricular (i.c.v.) injection of 6-hydroxydopamine (6-OHDA) prevented the antisecretory effect of the i.c.v. administration of PGE2, whereas pretreatment with 5,6-dihydroxytryptamine (5,6-DHT) plus p-chlorophenylalanine (PCPA) had no effect. I.c.v.-administered phentol...

  19. The Role of Conventional and Right-Sided ECG Screening for Subcutaneous ICD in a Tetralogy of Fallot Population.

    Science.gov (United States)

    Alonso, Pau; Osca, Joaquín; Cano, Oscar; Pimenta, Pedro; Andrés, Ana; Yagüe, Jaime; Millet, José; Rueda, Joaquín; Sancho-Tello, María José

    2017-02-01

    Information regarding suitability for subcutaneous implantable cardioverter-defibrillator (S-ICD) implant in tetralogy of Fallot (ToF) population is scarce and needs to be further explored. (1) to determine the proportion of patients with ToF eligible for S-ICD, (2) to identify the optimal sensing vector in ToF patients, (3) to test specifically the eligibility for S-ICD with right-sided screening, and (4) to compare with the proportion of eligible patients in a nonselected ICD population. We recruited 60 consecutive patients with ToF and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left arm and right arm electrodes 1 cm right lateral to the xiphoid midline. The Boston Scientific electrocardiogram (ECG) screening tool was utilized. We found a higher proportion of patients with right-sided positive screening in comparison with standard screening (77 ± 0.4% vs. 67 ± 0.4%; P right-sided screening (1.3 ± 1 vs. 1.1 ± 1 ms; P = 0.07). Patients who failed the screening had a longer QRS duration and longer QT interval. Standard and right-sided screening showed a higher percent of positive patients in the control group compared to ToF patients (P Right-sided screening was associated with a significant 10% increase in S-ICD eligibility in ToF patients. When comparing with an acquired cardiomyopathies group, ToF showed a lower eligibility for S-ICD. The most appropriate ECG vector was the alternate vector in contrast to what is observed in the general population. © 2017 Wiley Periodicals, Inc.

  20. Effects of REM sleep deprivation on sensorimotor gating and startle habituation in rats: role of social isolation in early development.

    Science.gov (United States)

    Chang, Hsin-An; Liu, Yia-Ping; Tung, Che-Se; Chang, Chuan-Chia; Tzeng, Nian-Sheng; Huang, San-Yuan

    2014-07-11

    The present study examined the role of rapid eye movement (REM) sleep on sensorimotor gating function in a developmentally rodent model of schizophrenic-spectrum disorders. Startle magnitude, prepulse inhibition (PPI) and startle habituation in an acoustic startle test were measured after 72-h of REM sleep deprivation (REMSD) in 14-week-old rats that were reared in one of the following conditions: control social interaction, 2-week isolation, and continuous isolation, since weaning. The results showed that REMSD significantly inhibited rats' PPI in socially controlled rats, and rats in two isolation groups appeared less sensitive to REMSD. After REMSD, startle habituation was significantly reduced in continuous-isolated rats but not in 2-week-isolated rats. These data indicate that REM sleep is essential for PPI; REMSD inhibits startle habituation in rats with continuous social isolation. In addition, social interaction, in early life or for the whole life, functions differently to the sensorimotor gating.

  1. Role of the metabolism of parathyroid hormone. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, Anne P. [Univ. of Rochester, NY (United States)

    1978-01-01

    The heterogeneity of parathyroid hormone (PTH) in plasma has prompted investigations of the metabolism of PTH and its relationship to hormone action. The time course of tissue distribution and metabolism of electrolytically iodinated PTH (E-PTH) previously shown to retain biological activity was compared with that of inactive PTH iodinated with Chloramine-T (CT-PTH). Labeled PTH (0.4 μg) was injected in the saphenous veins of anesthetized rats which were sacrificed at 1, 3, 5, 10, and 20 min. Tissue extracts from kidney, liver, and serum were chromatographed to separate intact PTH from its metabolites. In the kidney, the initial rate of degradation of E-PTH was greater than that of CT-PTH. The difference in initial rates of metabolism may be due, in part, to receptor-specific hydrolysis on peritubular cell membranes which selectively act on biologically active PTH molecules. PTH-responsive adenyl cyclase activity in isolated kidney cortex plasma membranes was measured and PTH metabolism was monitored simultaneously. When degradation was completely blocked by histone f3 (1 mg/ml), adenyl cyclase activity was significantly increased over control. In addition, when adenyl cyclase activity was negligible, the rate of PTH degradation by the membranes was not significantly diminished. Consistent with the in vivo data was the observation that E-PTH is metabolized by these membranes at a greater rate than CT-PTH. The data demonstrate the existence of a receptor-specific metabolism at sites which are independent of PTH receptor mediated adenyl cyclase activity.

  2. Role of neurotensin in radiation-induced hypothermia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A.; Harris, A.H. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1991-05-01

    The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin.

  3. Cypermethrin induced reproductive toxicity in male Wistar rats: protective role of Tribulus terrestris.

    Science.gov (United States)

    Sharma, Poonam; Huq, Amir Ul; Singh, Rambir

    2013-09-01

    The present study was designed to investigate role of ethanolic extract of Tribulus terrestris (EETT) against alpha-cypermethrin induced reproductive toxicity in male Wistar rats. 24 male Wistar rats weighing about 250-300g were divided in four groups. Group-I was control. alpha-cypermethrin (3.38 mg kg-1b.wt.) was given to group-IlI for 28 days. In Group-Ill, alpha-cypermethrin and EETT (100 mg kg -1b.wt.) were administered in combination for 28 days. Rats in group-IV were given EETT for 28 days. At the end of the experiment, rats were sacrificed, testes and epididymis were removed and sperm characteristics, sex hormones and various biochemical parameters were studied. Decrease in weight of testes and epididymis, testicular sperm head count, sperm motility, live sperm count, serum testosterone (T), follicle stimulating hormone (FSH), leutinizing hormone (LH), catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), total protein content and increase in sperm abnormalities and lipid peroxidation (LPO) level was observed in rats exposed to cypermethrin. In combination group-Ill, EETT treatment ameliorated alpha-cypermethrin induced damage. EETT treatment in group-IV increased testes and epididymis weight, sperm head counts, sperm motility, live sperm counts, testosterone, FSH, LH, GSH, CAT, SOD, GST, GR, GPx and total protein content. The study suggested that Tribulus terrestris plant possess reproductive system enhancement and antioxidant activity.

  4. A protective role of arecoline hydrobromide in experimentally induced male diabetic rats.

    Science.gov (United States)

    Saha, Indraneel; Das, Joydeep; Maiti, Biswaranjan; Chatterji, Urmi

    2015-01-01

    Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats. Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed. Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitated β-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2), were found to be activated by arecoline at the protein level. It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes.

  5. A Protective Role of Arecoline Hydrobromide in Experimentally Induced Male Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Indraneel Saha

    2015-01-01

    Full Text Available Objectives. Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats. Methods. Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed. Results. Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitated β-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1 and glucose transporter 2 (GLUT-2, were found to be activated by arecoline at the protein level. Conclusion. It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes.

  6. Circadian Rhythm Influences the Promoting Role of Pulsed Electromagnetic Fields on Sciatic Nerve Regeneration in Rats

    Science.gov (United States)

    Zhu, Shu; Ge, Jun; Liu, Zhongyang; Liu, Liang; Jing, Da; Ran, Mingzi; Wang, Meng; Huang, Liangliang; Yang, Yafeng; Huang, Jinghui; Luo, Zhuojing

    2017-01-01

    Circadian rhythm (CR) plays a critical role in the treatment of several diseases. However, the role of CR in the treatment of peripheral nerve defects has not been studied. It is also known that the pulsed electromagnetic fields (PEMF) can provide a beneficial microenvironment to quicken the process of nerve regeneration and to enhance the quality of reconstruction. In this study, we evaluate the impact of CR on the promoting effect of PEMF on peripheral nerve regeneration in rats. We used the self-made “collagen-chitosan” nerve conduits to bridge the 15-mm nerve gaps in Sprague-Dawley rats. Our results show that PEMF stimulation at daytime (DPEMF) has most effective outcome on nerve regeneration and rats with DPEMF treatment achieve quickly functional recovery after 12 weeks. These findings indicate that CR is an important factor that determines the promoting effect of PEMF on peripheral nerve regeneration. PEMF exposure in the daytime enhances the functional recovery of rats. Our study provides a helpful guideline for the effective use of PEMF mediations experimentally and clinically. PMID:28360885

  7. Role of thioredoxin nitration in bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Wang, Lei; Song, Yimin; Li, Xiankui; Guo, Haizhou; Zhang, Guojun

    2016-01-01

    Oxidant stimulation has been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our study aimed to investigate the role and mechanisms of thioredoxin (Trx) nitration during the development of IPF. A rat model of IPF was established by intratracheal instillation of bleomycin (BLM). Male Wistar rats were randomly distributed among the control group and BLM-treated group, in which rats were intratracheally instilled with a single dose of BLM (5.0 mg/kg body mass in 1.0 mL phosphate-buffered saline). At 7 or 28 days after instillation the rats were euthanized. Histopathological and biochemical examinations were performed. The activity and protein level of thioredoxin were assessed. The thioredoxin nitration level was determined using immunoprecipitation and immunoblotting techniques. Our results demonstrated that protein tyrosine nitration increased in the BLM-treated group compared with the control group. Trx activity decreased in the BLM group compared with control group, whereas Trx expression and nitration level increased dramatically in the BLM group compared with the control group. Our results indicated that Trx nitration might be involved in the pathogenesis of IPF.

  8. Purification and characterization of rat testicular glutathione S-transferases: role in the synthesis of eicosanoids

    Institute of Scientific and Technical Information of China (English)

    D.Anuradha; K.VeeraReddy; T.CharlesKumar; S.Neeraja; P.R.K.Reddy; P.Reddanna

    2000-01-01

    Aim: Purification of glutathione S-transferases (GSTs) from rat testis; separation and identification of various subunits and their role in eicosanoid biosynthesis. Methods: Purification of rat testicular GSTs by affinity chromatography, employing S-hexylglutathione-linked epoxy-activated Sepharose 6B column and separation of individual subunits by reverse phase-high pressure liquid chromatography (RP-HPLC). Characterization of affinity purified GSTs by Sodium dodecyl sulfate-polyacrylamide gel electlophoresis (SDS-PAGE) and Western blot analysis. The role of testicular GSTs in eicosanoid biosynthesis was determined by incubating GSTs with 5,6-Leukotriene A4Me (LTA4Me) and prostaglandin H2(PGH2) and analyzing the products formed on HPLC/TLC. Results: The present study reveals that majority of rat testicular GSTs are of Yb size (60%) with molecular weight of 27kDa. The most predominant subunits, however, are GST Yn2(27%), followed by GST Yc(24%) and GST Ynl(20%). These testicular GSTs showed very high Leukotriene C4(LTC4) synthase activity with 5,6-Leukotriene A4Me(LTA4Me) as the substrate and prostaglandin D (PGD) synthase activity with prostaglandin H2(PGH2) as the substrate. Conclusion: Majority of rat testicular GSTs are Yb sized and are involved in the synthesis of eicosanoids like LTC4 and PGD2.(Asian J Androl 2000 Dec;2:277-282)

  9. Role of shear-wave elastography (SWE) in complex cystic and solid breast lesions in comparison with conventional ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Bo Eun; Chung, Jin, E-mail: aqua0724@ewha.ac.kr; Cha, Eun-Suk; Lee, Jee Eun; Kim, Jeoung Hyun

    2015-07-15

    Highlights: • Complex cystic lesions have a broad spectrum of malignancy rate. • SWE is useful to evaluate cystic breast lesions. • Cutoff value of Emax was 108.5 kPa, for predicting malignancy. • Using this cutoff value, sensitivity of 86.7% and specificity of 97.3%. • SWE could reduce unnecessary biopsies in complex cystic and solid breast lesions. - Abstract: Objective: To evaluate the additional role of shear-wave elastography (SWE) in differential diagnosis of complex cystic and solid breast lesions. Materials and methods: From January 2013 to November 2013, 140 complex cystic and solid breast lesions from 139 consecutive patients were performed ultrasound and SWE prior to biopsy. BI-RADS ultrasound final assessment and SWE parameters were recorded for each lesion. Histopathologic diagnosis was used as the reference standard. Results: Among the 140 lesions, 30 lesions (21.4%) were malignant. The mean maximum elasticity (Emax) of malignant lesions (184.3 kPa) was significantly higher than that of benign lesions (45.5 kPa) (P < 0.001). Homogeneity of elasticity and color pattern were significantly different from malignancy and benign lesions (P < 0.05). Emax with cutoff value at 108.5 kPa showed Az value of 0.968 (95% CI, 0.932–0.985) with sensitivity of 86.7% and specificity of 97.3%. Using this cutoff value, false-positive rate was 2.7% and false-negative rate was 13.3%. By applying an Emax value of 108.5 kPa or less as a criterion for downgrading BI-RADS category 4a lesions to category 3 lesions, 103/123 (83.7%) lesions could be downgraded to category 3 lesions. Conclusion: Additional use of SWE could reduce unnecessary benign biopsies in complex cystic and solid breast lesions.

  10. The role of transforming growth factor alpha in rat craniofacial development and chondrogenesis.

    OpenAIRE

    Huang, L; Solursh, M; Sandra, A

    1996-01-01

    To explore the possible role of transforming growth factor alpha (TGF-alpha) in craniofacial development, its expression in the craniofacial region of rat embryos from embryonic day (d) 9 to d 20 was examined by in situ hybridisation and immunostaining. The TGF-alpha transcripts were first detected in the neural fold of embryonic d 9 and 10 embryos. In the craniofacial region, the TGF-alpha transcripts were not detected until embryonic d 16 in mesenchyme surrounding the olfactory bulb, within...

  11. Role of nitric oxide in experimental obliterative bronchiolitis (chronic rejection) in the rat.

    OpenAIRE

    Kallio, E A; Koskinen, P K; Aavik, E; Vaali, K; Lemstöm, K B

    1997-01-01

    The role of nitric oxide in obliterative bronchiolitis development, i.e., chronic rejection, was investigated in the heterotopic rat tracheal allograft model. An increase in the intragraft inducible nitric oxide synthase (iNOS) mRNA and mononuclear inflammatory cell iNOS immunoreactivity was demonstrated during progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared to syngeneic grafts. In nontreated allografts, however, intragraft nitric oxide produc...

  12. A new role for GABAergic transmission in the control of male rat sexual behavior expression.

    Science.gov (United States)

    Rodríguez-Manzo, Gabriela; Canseco-Alba, Ana

    2017-03-01

    GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons' activity. Blockade of VTA GABAA receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display. Copulation to satiety is characterized by the instatement of a long lasting (72h) sexual behavior inhibition and the mesolimbic system appears to be involved in this phenomenon. GABAergic transmission in the VTA might play a role in the maintenance of this long lasting sexual inhibitory state. To test this hypothesis, in the present work we investigated the effect of GABAA receptor blockade in sexually exhausted males 24h after copulation to satiety, once the sexual inhibitory state is established, and compared it with its effect in sexually experienced rats. Results showed that low doses of systemically administered bicuculline induced sexual behavior expression in sexually exhausted rats, but lacked an effect on copulation of sexually experienced animals. Intra-VTA bilateral infusion of bicuculline did not modify sexual behavior of sexually experienced rats, but induced sexual behavior expression in all the sexually exhausted males. Hence, GABA plays a role in the control of sexual behavior expression at the VTA. The role played by GABAergic transmission in male sexual behavior expression of animals with distinct sexual behavior conditions is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Cardioprotective role of tadalafil against cisplatin-induced cardiovascular damage in rats.

    Science.gov (United States)

    Saleh, Rasha M; Awadin, Walaa F; El-Shafei, Reham A; Elseady, Yousef Y; Wehaish, Faheim E; Elshal, Mohamed F

    2015-10-15

    The present study investigated the possible cardioprotective effect of tadalafil (Tad) on cisplatin (CDDP)-induced cardiac and vascular damages in rats. A total number of seventy two healthy male albino rats initially weighting between 200 and 220 g were used and randomly divided into four groups,18 rats in each. The control group received no treatment; CDDP group received a single dose of CDDP (4 mg/kg) intraperitoneal (i.p.) per week for 4 weeks the duration of the experiment; Tad group received 0.4 mg/kg BW Tad i.p. daily and Tad +CDDP group received 0.4 mg/kg BW Tad i.p. +4 mg/kg BW CDDP i.p. The results showed that Tad was able to decrease blood pressure, heart rate, levels of serum cardiac troponin (cTn-I), malondialdehyde (MDA) and increased levels of reduced glutathione (GSH) and nitric oxide (NO) in the heart homogenate sample from CDDP treated rats. Semi-quantitative analysis showed that Tad was able to decrease the histopathological scores of cardiac muscular hyalinzation and fibrosis in three sacrifices in CDDP treated rats. CDDP treated rats showed significantly increased thickening in wall of aorta with an irregular luminal layer of endothelial cell linings in three sacrifices when it was compared to other groups. Moreover, immunohistochemical labeling of α- smooth muscle actin (α-SMA) in aorta revealed significant lower scores in Tad +CDDP group when they were compared to CDDP group. In conclusion, Tad alone did not induce any harmful effects on blood pressure, selective antioxidant, peroxidation markers or cardiac histology, in addition, Tad has a cardio-protective role against CDDP.

  14. Antioxidant role of heme oxygenase-1 in prehepatic portal hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Soledad Gonzales; María Julia Pérez; Juan C Perazzo; María Luján Tomaro

    2006-01-01

    AIM: To study the effect of bilirubin on the oxidative liver status and the activity and expression of heme oxygenase-1 (HO-1) in rat liver injury induced by prehepatic portal hypertension.METHODS: Wistar male rats, weighing 200-250 g, were divided at random into two groups: one group with prehepatic portal hypertension (PH) induced by regulated prehepatic portal vein ligation (PPVL) and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes,HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured.RESULTS: In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances (TBARS) content and a decrease in reduced glutathione (GSH) levels. The activities of liver antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin (5 μmol/kg body weight) 24 h before the end of the experiment entirely prevented ali these effects. Pretreatment with Sn-protoporphyrin Ⅸ (Sn-PPIX) (100 μg/kg body weight, i.p.),a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides,carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect.CONCLUSION: These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.

  15. The role of glutathione and cysteine conjugates in the nephrotoxicity of o-xylene in rats

    Energy Technology Data Exchange (ETDEWEB)

    Morel, G.; Bonnet, P.; Cossec, B.; Morel, S.; Cour, C.; Lambert, A.M.; Roure, M.B.; Brondeau, M.T. [Institut National de Recherche et de Securite, 54 - Vandoeuvre (France)

    1998-09-01

    Moderate nephrotoxicity was induced in male and female rats exposed to o-xylene for 4 h at atmospheric concentrations of {proportional_to}3000 ppm. The xylene in vivo nephrotoxicity resulted in low enzyme leakage from the kidney into the urine. This low leakage was confirmed in 24-h urine by an increase in {gamma}-glutamyltranspeptidase ({gamma}GT), N-acetyl-{beta}-d-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities. Compared to the control, both the 24-h urine output and the glucose excretion increased in male and female rats. These increases were probably a result of damage to the renal proximal tubules. The role of the metabolic pathway of glutathione in the emergence of the renal damage observed with o-xylene was investigated in rats. Recent studies indicate that the metabolic pathway of glutathione may be a bioactivation pathway, which is responsible for nephrotoxic effects with several drugs or chemicals. The renal toxicity of three synthesized o-xylene thio-conjugates was investigated in several groups of female rats. Administration of S-(o-methylbenzyl)glutathione (i.p., 1 mmol/kg), S-(o-methylbenzyl)cysteine (per os, 1 mmol/kg) or N-acetyl-S-(o-methylbenzyl)cysteine (i.p., 0.75 mmol/kg) to female rats did not induce renal toxicity, as monitored by urinary biochemical parameters ({gamma}GT, NAG, ALP, glucose). The data obtained suggest that the glutathione pathway would appear to be only detoxication, and probably does not contribute to the renal toxicity of o-xylene in female rats. Thus, either another metabolic pathway or other intermediate metabolites are probably involved in the nephrotoxic action of o-xylene. (orig.) (orig.) With 2 figs., 1 tab., 23 refs.

  16. The role of glutathione and cysteine conjugates in the nephrotoxicity of o-xylene in rats.

    Science.gov (United States)

    Morel, G; Bonnet, P; Cossec, B; Morel, S; Cour, C; Lambert, A M; Roure, M B; Brondeau, M T

    1998-09-01

    Moderate nephrotoxicity was induced in male and female rats exposed to o-xylene for 4 h at atmospheric concentrations of approximately 3000 ppm. The xylene in vivo nephrotoxicity resulted in low enzyme leakage from the kidney into the urine. This low leakage was confirmed in 24-h urine by an increase in gamma-glutamyltranspeptidase (gammaGT), N-acetyl-beta-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities. Compared to the control, both the 24-h urine output and the glucose excretion increased in male and female rats. These increases were probably a result of damage to the renal proximal tubules. The role of the metabolic pathway of glutathione in the emergence of the renal damage observed with o-xylene was investigated in rats. Recent studies indicate that the metabolic pathway of glutathione may be a bioactivation pathway, which is responsible for nephrotoxic effects with several drugs or chemicals. The renal toxicity of three synthesized o-xylene thio-conjugates was investigated in several groups of female rats. Administration of S-(o-methylbenzyl)glutathione (i.p., 1 mmol/kg), S-(o-methylbenzyl)cysteine (per os, 1 mmol/kg) or N-acetyl-S-(o-methylbenzyl)cysteine (i.p., 0.75 mmol/kg) to female rats did not induce renal toxicity, as monitored by urinary biochemical parameters (gammaGT, NAG, ALP, glucose). The data obtained suggest that the glutathione pathway would appear to be only detoxication, and probably does not contribute to the renal toxicity of o-xylene in female rats. Thus, either another metabolic pathway or other intermediate metabolites are probably involved in the nephrotoxic action of o-xylene.

  17. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Energy Technology Data Exchange (ETDEWEB)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

    2014-07-15

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  18. Protective Effects of Acupuncture Against Gentamicin-Induced Ototoxicity in Rats: Possible Role of Neurotrophin-3

    Science.gov (United States)

    Zhou, Ping; Ma, Weijun; Sheng, Ying; Duan, Maoli; Zhang, Xiaotong

    2017-01-01

    Background The aim of this study was to investigate the protective effects of acupuncture against gentamicin-induced ototoxicity and explore the possible protective role of neurotrophin-3 (NT-3). Material/Methods Twenty-four rats were divided randomly into 4 groups: control group, gentamicin group, neitinggong group, and tinggong group. Rats in the gentamicin, neitinggong, and tinggong groups received intraperitoneal injection of gentamicin (100 mg/kg) for 14 consecutive days. Rats in the neitinggong and tinggong groups further received acupuncture at neitinggong or tinggong acupoints once every 2 days for 20 days. Rats in the control group received intraperitoneal injection of saline. Auditory brainstem response (ABR) was tested in all rats on the day before treatment (day 0), and again on day 14 and day 20 to determine the average threshold value of ABR for each treatment group. The expression of NT-3 in the cochlear nucleus and the inferior colliculus nucleus were detected by immunohistochemical staining. Results The average threshold value of ABR was significantly higher in the gentamicin group as compared with that of the control group on day 14 (P0.05). However, the expression of NT-3 in the inferior colliculus nucleus in both the neitinggong and tinggong groups was significantly higher than that of the gentamicin group (P<0.01). Conclusions A decrease in NT-3 expression in the inferior colliculus nucleus may contribute to gentamicin-induced ototoxicity in rats. Acupuncture at neitinggong or tinggong acupoints effectively improved hearing, which was attributed partially to the rescue of NT-3 expression in the inferior colliculus nucleus. Therefore, preserving NT-3 expression in the auditory system may be a viable strategy to counteract gentamicin-induced ototoxicity. PMID:28121979

  19. Innovation in vegetable seed production and the role of consumers in the organic and conventional babyleaf chains: The case of Denmark

    DEFF Research Database (Denmark)

    Deleuran, Lise Christina

    2011-01-01

    , aspects of preference for local vegetable products were investigated. The methodological approach has been in the form of two questionnaires presented to consumers in two different chain structures, an industrialized chain (linking actors from ‘farm to fork’) and an alternative chain where organic produce...... is delivered to the consumers' doorstep through a box-scheme concept. The participants in the surveys were selected to identify elements that potentially could be used as a spur in innovation and development of new products in the chain and not necessarily to indicate general consumer interests. The overall...... step in the babyleaf chain. Dialog among the actors in the chain is essential to meet the consumer demands from both a conventional and an organic perspective. The role of organic seed in organic vegetable productions is discussed....

  20. Role of connective tissue growth factor in experimental radiation nephropathy in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Dian-ge; WANG Tie-min

    2008-01-01

    Background Connective tissue growth factor (CTGF) is a potent fibrogenic cytokine which has been associated with progressive glomerulosclerosis and tubulointerstitial fibrosis. We investigated the role of CTGF on the progression of a rat model of radiation nephropathy.Methods The model of radiation nephropathy in rats was established as follows: control group (n=-12), underwent only laparotomy; irradiated group (n=20), underwent a laparotomy, then the rats were subjected to a single dose 25 Gy X-ray to the kidneys. The rats were followed up one, three, six and nine months after renal exposure to radiation.Results Renal dysfunction was noted early in irradiated rats. Histological analysis showed focal glomerular sclerotic lesions at an early stage after irradiation. Radiation-induced glomerular and tubulointerstitial injudes were particularly severe the sixth month after irradiation as compared to the control group (P <0.01). By immunohistochemistry, increased expression of CTGF was noted in the irradiated kidneys, which began to increase from the first month after irradiation,and remained significantly higher at the sixth and ninth month after irradiation (P <0.01). Upon Westem blot analysis CTGF protein expression showed an increase in the radiation treated kidneys compared with the control rats. The expression of CTGF closely correlated with the progression of radiation nephropathy. The expression of α-smooth muscle actin, vimentin, type Ⅲ collagen and type Ⅳ collagen was also high in the irradiated kidney as compared to control rat kidneys (P <0.05), and was most severe at the sixth and ninth month after irradiation (P <0.01). By double immunostaining, CTGF expressing cells were found to be α-SMA-positive myofibroblasts and vimentin-positive tubular epithelial cells. Glomerular expression of CTGF closely correlated with the glomerular expression of α-SMA (r=0.628, P <0.01), vimentin (r=0.462, P <0.05) and accumulation of type Ⅳ collagen (r=0.584, P <0

  1. The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

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    Vafaei A.L.

    2008-03-01

    Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

  2. Role of vascular peroxidase 1 in senescence of endothelial cells in diabetes rats.

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    Liu, Si-Yu; Yuan, Qiong; Li, Xiao-Hui; Hu, Chang-Ping; Hu, Rong; Zhang, Guo-Gang; Li, Dai; Li, Yuan-Jian

    2015-10-15

    Reactive oxygen species (ROS) is thought as a major reason of vascular injury in diabetes. Vascular peroxidase 1 (VPO1) is a newly found peroxidase playing an important role in inducing oxidative stress. In the present experiment, we tested the role of VPO1 in senescence of endothelial cells in streptozotocin (STZ)-induced diabetic rats and cultured endothelial cells. Blood samples were collected from carotid arteries. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were measured, serum concentration of glucose, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and the expression of VPO1 in the aorta were determined. Endothelial cells were treated with high glucose or H2O2, the concentrations of MCP-1, TNF-α and hypochlorous acid (HOCl) and the expression of VPO1 were determined. shRNA of VPO1 was used for mechanism research in cultured cells. Vasodilator responses to Ach were impaired markedly and the serum concentrations of glucose, TNF-α and MCP-1 were significantly increased in diabetic rats. The expression of VPO1 in the aorta was upregulated in diabetic rats. High glucose treatment significantly decreased cell viability and elevated the levels of MCP-1, TNF-α and HOCl and upregulated the expression of VPO1. H2O2 treatment significantly induced cellular senescence, inhibited eNOS expression and NO production. The effects of high glucose and H2O2 were attenuated by shRNA interference of VPO1. VPO1 plays an important role in senescence of endothelial cells and endothelial dysfunction by induction of oxidative stress and inflammatory reaction in type 2 diabetic rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

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    Gao, Meiya; Long, Hu; Ma, Wenqiang; Liao, Lina; Yang, Xin; Zhou, Yang; Shan, Di; Huang, Renhuan; Jian, Fan; Wang, Yan; Lai, Wenli

    2016-12-01

    This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3(-/-)) mice. Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. Role of articular disc in cartilaginous growth of the mandible in rats

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    Fang Xiao

    2017-01-01

    Full Text Available Displacement of the temporomandibular joint (TMJ disc causes a lateral shift of the mandible and less-developed and/or distally located mandible unilaterally and bilaterally, respectively, if occurred in growing individuals. The purpose of this study was to evaluate mandibular condylar growth in growing rats after TMJ discectomy and to explore a certain significant role of articular disc in the TMJ in mandibular or cartilaginous growth. Eighteen 4-week-old Wistar strain male rats were divided into two groups with nine in each group, i.e., rats with TMJ discectomy (discectomy group and only sham operation (control group. Four weeks after initiating the experiment, morphometric analyses of the mandible were performed using a rat and mouse cephalometer and micro-computed tomography. Then, the mandibular condyles were subjected to histomorphometric analyses. Condylar and mandibular growth was reduced significantly in the discectomy group than in the control group. In the discectomy group, the condyle also became flatter and smaller. In addition, the 4-layer structure of condylar cartilage was unclear with thicker fibrous and thinner lower hypertrophic layers in the discectomy group when compared to the controls. It is shown that resection of the articular disc substantially affects condylar and mandibular growth in terms of the cartilaginous growth, suggesting that TMJ disc is indispensable for maintaining normal growth of the condyle and mandible, leading to optimal development of the TMJ and the entire mandible.

  5. Rats' urinary metabolomes reveal the potential roles of functional foods and exercise in obesity management.

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    Farag, Mohamed A; Ammar, N M; Kholeif, T E; Metwally, N S; El-Sheikh, N M; Wessjohann, Ludger A; Abdel-Hamid, A Z

    2017-03-22

    The complexity of the metabolic changes in obese individuals still presents a challenge for the understanding of obesity-related metabolic disruptions and for obesity management. In this study, a gas chromatography mass spectrometry (GC-MS) based metabolomics approach targeting urine metabolism has been applied to assess the potential roles of functional foods and exercise for obesity management in rats. Male albino rats diagnosed as obese via histopathology and biochemical assays were administered functional foods in common use for obesity management including pomegranate, grapefruit, and red cabbage juice extracts in parallel with swimming exercise. Urine samples were collected from these rats, and likewise from healthy control animals, for metabolite analysis using (GC-MS) coupled to multivariate data analysis. The results revealed a significant elevation in oxalate and phosphate levels in obese rat urine concurrent with lower lactate levels as compared to the control group. Furthermore, and to pinpoint the bioactive agents in the administered functional foods, ultra performance liquid chromatography (UPLC) coupled to high resolution time-of-flight mass spectrometry (TOF-MS) was employed for secondary metabolite profiling. The different phenolic classes found in the examined functional foods, viz. ellagitannins in pomegranate, flavanones in grapefruit and flavonols in red cabbage, are likely to mediate their anti-obesity effects. The results indicate that these functional foods and exercise were quite effective in reverting obesity-related metabolic disruptions back to normal status, as revealed by orthogonal partial least squares-discriminant analysis (OPLS-DA).

  6. Roles of Fatty Acid oversupply and impaired oxidation in lipid accumulation in tissues of obese rats.

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    Oakes, Nicholas D; Kjellstedt, Ann; Thalén, Pia; Ljung, Bengt; Turner, Nigel

    2013-01-01

    To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studied in vivo fatty acid (FA) metabolism in obese (Obese) and lean (Lean) Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-(3)H]-(R)-2-bromopalmitate ((3)H-R-BrP) and [U-(14)C]-palmitate ((14)C-P) FA tracers, respectively. Whole-body FA appearance (R a ) was estimated from plasma (14)C-P kinetics. Whole-body FA oxidation rate (R ox) was assessed using (3)H2O production from (3)H-palmitate infusion, and tissue FA oxidative capacity was evaluated ex vivo. In the basal fasting state Obese had markedly elevated FA levels and R a , associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid, R ox was lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply.

  7. Roles of Fatty Acid Oversupply and Impaired Oxidation in Lipid Accumulation in Tissues of Obese Rats

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    Nicholas D. Oakes

    2013-01-01

    Full Text Available To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studied in vivo fatty acid (FA metabolism in obese (Obese and lean (Lean Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-3H]-(R-2-bromopalmitate (3H-R-BrP and [U-14C]-palmitate (14C-P FA tracers, respectively. Whole-body FA appearance (Ra was estimated from plasma 14C-P kinetics. Whole-body FA oxidation rate (Rox was assessed using 3H2O production from 3H-palmitate infusion, and tissue FA oxidative capacity was evaluated ex vivo. In the basal fasting state Obese had markedly elevated FA levels and Ra, associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid, Rox was lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply.

  8. [Role of renal sympathetic nerve and oxidative stress in foot shock-induced hypertension in rats].

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    Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Dong, Tao; Zhang, Guo-Xing

    2015-06-25

    The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups (the number of each group was 15): control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve + foot shock group, Tempol treatment + foot shock group, denervation of renal sympathetic nerve + Tempol treatment + foot shock group. Rats were received electrical foot shock for 14 days (2-4 mA, 75 V, shocks of 50-100 ms every 30 s, for 4 h each session through an electrified grid floor every day). Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats (rats were allowed to recover for one week before the beginning of the foot shock procedure). The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance (TBARS), renin, angiotensin II (AngII) and glutathione peroxidase (GSH-Px) in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased (P indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced.

  9. Neuroprotective and antioxidant role ofPhoenix dactylifera in permanent bilateral common carotid occlusion in rats

    Institute of Scientific and Technical Information of China (English)

    Rohini R Pujari; Neeraj S Vyawahare; Prasad A Thakurdesai

    2014-01-01

    Objective:To investigate neuroprotective and antioxidant effect ofPhoenix dactylifera (P. dactylifera)(PD) fruits.Methods:Methanolic extract ofP. dactylifera fruits(MEPD) at doses of 30,100 and300 mg/kg was studied against permanentBCCAO(long-term hypoperfusion) in rats. Chronic occlusion of bilateral common carotid arteries(BCCA) caused significant elevation in malondialdehyde levels due to increased lipid peroxidation as well as decrease in levels of other biochemical enzymesi.e. glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferse, catalase and superoxide dismutase.Results:Post occlusion treatment for15 d with 100 and300 mg/kg doses ofMEPD significantly reduced the enhanced malondialdehyde levels and reversed the alterations in the declined levels of antioxidant enzymes in brain homogenates of hypoperfused rats.Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and restlessness(open field paradigm) accompanied by deficits of spatial learning and memory(Morris water maze testing).Additionally, histopathological observations in hypoperfused brains revealed reactive changes like shrinkage and necrosis of neurons.100 and300 mg/kg doses ofMEPD significantly alleviated these alterations.Conclusions:These results confirmed the protective role ofP. dactylifera in ischemia hypoperfusion and thereby it’s beneficial role in cerebrovascular insufficiency states and related complications.

  10. Representation of actions in rats: the role of cerebellum in learning spatial performances by observation.

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    Leggio, M G; Molinari, M; Neri, P; Graziano, A; Mandolesi, L; Petrosini, L

    2000-02-29

    Experimental evidence demonstrates that cerebellar networks are involved in spatial learning, controlling the acquisition of exploration strategies without blocking motor execution of the task. Action learning by observation has been considered somehow related to motor physiology, because it provides a way of learning performances that is almost as effective as the actual execution of actions. Neuroimaging studies demonstrate that observation of movements performed by others, imagination of actions, and actual execution of motor performances share common neural substrates and that the cerebellum is among these shared areas. The present paper analyzes the effects of observation in learning a spatial task, focusing on the cerebellar role in learning a spatial ability through observation. We allowed normal rats to observe 200 Morris water maze trials performed by companion rats. After this observation training, "observer" rats underwent a hemicerebellectomy and then were tested in the Morris water maze. In spite of the cerebellar lesion, they displayed no spatial defects, exhibiting exploration abilities comparable to controls. When the cerebellar lesion preceded observation training, a complete lack of spatial observational learning was observed. Thus, as demonstrated already for the acquisition of spatial procedures through actual execution, cerebellar circuits appear to play a key role in the acquisition of spatial procedures also through observation. In conclusion, the present results provide strong support for a common neural basis in the observation of actions that are to be reproduced as well as in the actual production of the same actions.

  11. Mitigating Role of Quercetin Against Cyclophosphamide-Induced Lung Injury in Rats

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    Nora A. Asry

    2014-05-01

    Full Text Available Quercetin (Qur, a polyphenolic flavonoid compound present in large amounts in vegetables and fruits, plays important roles in human health through its antioxidant activity. This study was conducted to investigate the possible modulatory effect of Qur against cyclophosphamide (CP-induced lung oxidative damage and to highlight the underlying mechanisms of such effect. Male Sprague-Dawely rats were divided into four groups. Group I was control. Group II received Qur (100 mg/kg/d. p.o. for 14 consecutive days. Group III was injected once with CP (150 mg/kg, i.p.. Group IV received Qur for 7 consecutive days, before and after CP injection.A single i.p. injection of CP markedly increased the level of serum biomarkers; total protein, LDH. Cyclophosphamide significantly increased the lung content of lipid peroxides and decreased levels of reduced glutathione. Treatment of rats with Qur for 7 days prior to and 7 days after cyclophosphamide significantly ameliorated the alterations in lung and serum biomarkers associated with inflammatory reactions. Moreover, Qur attenuated the secretion of pro-inflammatory cytokine, TNF-α in rat serum. In addition, Qur slightly ameliorated CP-induced histopathological changes in lung tissue. Our results suggest that Qur produces a protective effect against CP-induced lung injury and suggest a role of oxidative stress and inflammation in the pathogenesis.

  12. Role of sympathetic nervous system in rat model of chronic visceral pain.

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    Gil, D W; Wang, J; Gu, C; Donello, J E; Cabrera, S; Al-Chaer, E D

    2016-03-01

    Changes in central pain modulation have been implicated in generalized pain syndromes such as irritable bowel syndrome (IBS). We have previously demonstrated that reduced descending inhibition unveils a role of sympathoneuronal outflow in decreasing peripheral sensory thresholds, resulting in stress-induced hyperalgesia. We investigated whether sympathetic nervous system (SNS) exacerbation of pain sensation when central pain inhibition is reduced is relevant to chronic pain disorders using a rat colon irritation (CI) model of chronic visceral hypersensitivity with hallmarks of IBS. Rats were treated to a series of colorectal balloon distensions (CRD) as neonates resulting in visceral and somatic hypersensitivity and altered stool function that persists into adulthood. The visceral sensitivity was assessed by recording electromyographic (EMG) responses to CRD. Somatic sensitivity was assessed by paw withdrawal thresholds to radiant heat. The effects on the hypersensitivity of (i) inhibiting sympathoneuronal outflow with pharmacological and surgical interventions and (ii) enhancing the outflow with water avoidance stress (WAS) were tested. The alpha2-adrenergic agonist, clonidine, and the alpha1-adrenergic antagonist, prazosin, reduced the visceral hypersensitivity and WAS enhanced the pain. Chemical sympathectomy with guanethidine and surgical sympathectomy resulted in a loss of the chronic visceral hypersensitivity. The results support a role of the SNS in driving the chronic visceral and somatic hypersensitivity seen in CI rats. The findings further suggest that treatments that decrease sympathetic outflow or block activation of adrenergic receptors on sensory nerves could be beneficial in the treatment of generalized pain syndromes. © 2015 John Wiley & Sons Ltd.

  13. The role of hypothalamus tuberomammillary nucleus on the regulation of respiratory movement of rats with asthma

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    Chen CHEN

    2016-01-01

    Full Text Available Objective  To explore the role of central histaminergic neurons in the tuberomammillary nucleus (TMN of posterior hypothalamus on asthma. Methods  Seventy-two healthy male SD rats were served as study objects. Sixty-four rats were sensitized with ovalbumin (OA solution intraperitoneally and challenged with OA aerosol inhalation to prepare asthma model. Asthma attack was evoked in asthmatic rats by OA solution injected intravenously, the electrical activities of TMN in posterior hypothalamus were recorded with biological signal collecting system and the power spectra were analyzed. TMN was lesioned or stimulated electrically by central stereo positioning technology. Histamine H3 receptor agonist R-(α-methylhistamine (RMHA or antagonist thioperamide (THIO was microinjected into TMN by central nuclear group microinjection technology, and the pulmonary function indexes were detected including diaphragm electromyography (EMGdi frequency, EMGdi integral, minute ventilation volume (MVV, expiratory time/inspiratory time (TE/TI, airway resistance (Raw and dynamic pulmonary compliance (Cdyn. Results  Compared with control group, the percentage of α, β1 and β2 wave in the electrical activities of TMN of asthmatic rats increased significantly, while the percentage of δ and θ wave decreased and the total discharge power increased. Compared with the corresponding control group, electric lesion of TMN or TMN microinjected with histamine H3 receptor antagonist increased EMGdi frequency, TE/TI, Raw, and decreased EMGdi integral, MVV and Cdyn. Compared with the corresponding control group, electric stimulation of TMN or TMN microinjected with histamine H3 receptor agonist decreased EMGdi frequency, TE/TI, Raw, and increased EMGdi integral, MVV and Cdyn. Conclusion  Central histaminergic neurons in tuberomammillary nucleus of posterior hypothalamus are activated in asthmatic rats. DOI: 10.11855/j.issn.0577-7402.2015.12.09

  14. Healing of colonic ischemic anastomoses in the rat: role of superoxide radicals.

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    Garcia, J G; Criado, F J; Persona, M A; Alonso, A G

    1998-07-01

    The aim of this study was to evaluate the role of superoxide radicals in the healing of ischemic colonic anastomoses in the rat. Adult male Wistar rats were used in a factorial design with two factors (normal or ischemic colonic anastomoses) each having two levels (treatment with saline or allopurinol). Colonic anastomoses were performed either in normal or previously devascularized colons (ischemic anastomoses) at identical locations, using the same technique. On the fourth postoperative day, animals were killed, and specimens were taken for determinations. Ischemic anastomoses displayed significant increases in superoxide radical (assayed as superoxide anion), superoxide dismutase, and glutathione peroxidase concentrations. Bursting strength and hydroxyproline levels were also significantly lower in these anastomoses. Allopurinol administration elicited a significant decrease in superoxide anions and raised both bursting strength and hydroxyproline levels only in ischemic anastomoses. Superoxide radicals are involved in the delay in healing of ischemic anastomoses. Allopurinol lowers superoxide anion production and has beneficial effects on the cicatrization of ischemic anastomoses.

  15. Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats

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    Jian-hua Liu

    2012-01-01

    Full Text Available Adenylyl cyclase (AC-cyclic adenosine monophosphate (cAMP-cAMP-dependent protein kinase A (PKA cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA treatment for chronic mild stress (CMS-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.

  16. Locus coeruleus lesions and PCOS: role of the central and peripheral sympathetic nervous system in the ovarian function of rat

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    Farideh Zafari Zangeneh

    2012-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction”. “Autonomic and central nervous systems play important roles in the regulation of ovarian physiology”. The noradrenergic nucleus locus coeruleus (LC plays a central role in the regulation of the sympathetic nervous system and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway and its activation is essential to trigger spontaneous or induced LH surges. This study evaluates sympathetic outflow in central and peripheral pathways in PCO rats. Objective: Our objectives in this study were (1 to estimate LC activity in rats with estradiol valerate (EV-induced PCO; (2 to antagonized alpha2a adrenoceptor in systemic conditions with yohimbine. Materials and Methods: Forty two rats were divided into two groups: 1 LC and yohimbine and 2 control. Every group subdivided in two groups: eighteen rats were treated with estradiol valerate for induction of follicular cysts and the remainders were sesame oil groups. Results: Estradiol concentration was significantly augmented by the LC lesion in PCO rats (p<0.001, while LC lesion could not alter serum concentrations of LH and FSH, like yohimbine. The morphological observations of ovaries of LC lesion rats showed follicles with hyperthecosis, but yohimbine reduced the number of cysts, increased corpus lutea and developed follicles. Conclusion: Rats with EV-induced PCO increased sympathetic activity. LC lesion and yohimbine decreased the number of cysts and yohimbine increased corpus lutea and developed follicles in PCO rats.

  17. The role of Na(+), K(+)-ATPase in the hypoxic vasoconstriction in isolated rat basilar artery.

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    Shen, Haitao; Liang, Peng; Qiu, Suhua; Zhang, Bo; Wang, Yongli; Lv, Ping

    2016-06-01

    Hypoxia-induced cerebrovascular dysfunction is a key factor in the occurrence and the development of cerebral ischemia. Na(+), K(+)-ATPase affects the regulation of intracellular Ca(2+) concentration and plays an important role in vascular smooth muscle function. However, the potential role of Na(+), K(+)-ATPase in hypoxia-induced cerebrovascular dysfunction is unknown. In this study, we found that the KCl-induced contraction under hypoxia in rat endothelium-intact basilar arteries is similar to that of denuded arteries, suggesting that hypoxia may cause smooth muscle cell (SMC)-dependent vasoconstriction in the basilar artery. The Na(+), K(+)-ATPase activity of the isolated basilar artery with or without endothelium significantly reduced with prolonged hypoxia. Blocking the Na(+)-Ca(2+) exchanger with Ni(2+) (10(-3)M) or the L-type Ca(2+) channel with nimodipine (10(-8)M) dramatically attenuated KCl-induced contraction under hypoxia. Furthermore, prolonged hypoxia significantly reduced Na(+), K(+)-ATPase activity and increased [Ca(2+)]i in cultured rat basilar artery SMCs. Hypoxia reduced the protein and mRNA expression of the α2 isoform of Na(+), K(+)-ATPase in SMCs in vitro. We used a low concentration of the Na(+), K(+)-ATPase inhibitor ouabain, which possesses a high affinity for the α2 isoform. The contractile response in the rat basilar artery under hypoxia was partly inhibited by ouabain pretreatment. The decreased Na(+), K(+)-ATPase activity in isolated basilar artery and the increased [Ca(2+)]i in SMCs induced by hypoxia were partly inhibited by pretreatment with a low concentration of ouabain. These results suggest that hypoxia may educe Na(+), K(+)-ATPase activity in SMCs through the α2 isoform contributing to vasoconstriction in the rat basilar artery.

  18. Monoamine concentrations changes in the PTU-induced hypothyroid rat brain and the ameliorating role of folic acid.

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    Tousson, E; Ibrahim, W; Arafa, N; Akela, M A

    2012-03-01

    Thyroid hormones are recognized as the key metabolic hormones that play a critical role in the development of central nervous system (CNS) throughout life. The present study was designed to determine the changes in brain monoamine concentrations in 6-n-propyl thiouracil (PTU)-induced hypothyroid rats, in addition to the ameliorating role of folic acid treatment. Fifty male albino rats were equally divided into five groups; first and second groups were the control and folic acid groups, respectively, while the third group was the hypothyroid group in which the rats received PTU in drinking water for 6 weeks. The fourth and fifth groups were co- and post-treated folic acid groups with hypothyroid rats, respectively. Our results revealed that serotonin and norepinephrine concentrations were significantly decreased in the hypothalamus and cortex, while it significantly increased in the hippocampus of hypothyroid rats when compared with control group. Serotonin and norepinephrine concentrations were decreased in hypothalamus and cortex in co- and post-treated folic acid groups with hypothyroid rats, while the concentration of dopamine were significantly increased in the hypothalamus and hippocampus of the hypothyroid rats and co-treated folic acid group with hypothyroid rats. In cortex, the dopamine concentration was significantly increased in hypothyroid rats and post-treated folic acid group with hypothyroid rats, while it significantly decreased in co-treated folic acid group with hypothyroid rats when compared with the control group. Also, our results revealed that, folic acid treatment was better if it is administered as an adjuvant after returning to the euthyroid state by withdrawing PTU from the drinking water.

  19. Protective role of metallothionein in stress-induced gastric ulcer in rats

    Institute of Scientific and Technical Information of China (English)

    Ping Jiang; Lin Chang; Chun-Shui Pan; Yong-Fen Qi; Chao-Shu Tang

    2005-01-01

    AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnSO4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress

  20. The role of autophagy in lung ischemia/reperfusion injury after lung transplantation in rats

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    Liu, Sheng; Zhang, Jun; Yu, Bentong; Huang, Lei; Dai, Bin; Liu, Jichun; Tang, Jian

    2016-01-01

    Background: The aim of this study was to explore the role of autophagy in the cold I/R injury following lung transplantation. Methods: The rat orthotopic lung transplantation model was established to perform the level of autophagy in the cold I/R injury in this study. The pretreatment of inhibitor (3-Methyladenine [3-MA]) and activator (rapamycin [RAPA]) of autophagy were performed to assess the role of autophagy in the cold I/R injury following lung transplantation in rats. Results: After lung transplantation, the autophagy, lung cell apoptosis and lung injury were aggravated and peaked at 6 h following the transplantation. The inhibition of autophagy by 3-MA induced downregulated of autophagy, decreased cell apoptosis. Meanwhile, the lung injury, which was indicated by calculating the peak inspiratory pressure (PIP), pulmonary vein blood gas analysis (PO2) and ratio of wet to dry in lung (W/D), was ameliorated after treatment with 3-MA. The activation of autophagy by RAPA causing the upregulated of autophagy and apoptosis of lung cells, and enhanced the lung injury. Conclusion: All the results suggested that the autophagy was involved in the cold I/R injury in lung transplantation model, and played a potential role on the regulation of I/R injury after lung transplantation. PMID:27648150

  1. The kidneys play a central role in the clearance of rhGH in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads;

    2016-01-01

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted...... at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rh...

  2. Role of angiotensin-converting enzyme inhibitor, lisinopril, on spermatozoal functions in rats.

    Science.gov (United States)

    Saha, L; Garg, S K; Bhargava, V K; Mazumdar, S

    2000-04-01

    Angiotensin-converting enzyme is present in the male reproductive system but its role in the physiology of reproduction is not known. To see the effect of angiotensin-converting enzyme on spermatozoal functions, lisinopril, an angiotensin-converting enzyme inhibitor, was administered orally using two different doses (10 and 20 mg/kg/day) to rats. Both short-term (2 weeks) and long-term (6 weeks) effects of the drug were observed. Lisinopril treatment resulted in a marked decrease in sperm density, sperm motility and zona pellucida penetration. Acrosome reaction by spermatozoa obtained from drug-treated animals was significantly lower when compared with spermatozoa from normal animals.

  3. The role of contextual conditioning in the effect of reinforcer devaluation on instrumental performance by rats.

    Science.gov (United States)

    Jonkman, Sietse; Kosaki, Yutaka; Everitt, Barry J; Dickinson, Anthony

    2010-03-01

    Different groups of rats received different amounts of training to lever press for a food reinforcer before an aversion was conditioned to the food. This devaluation of the reinforcer reduced responding in both subsequent extinction and reinforced tests of responding to a degree that was independent of the amount of instrumental training. Moreover, interpolating context extinction between aversion conditioning and the extinction test reduced the magnitude of the devaluation effect, thereby indicating that Pavlovian contextual conditioning may play a role in the instrumental devaluation effect.

  4. Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution.

    Science.gov (United States)

    Koning, Nick J; de Lange, Fellery; Vonk, Alexander B A; Ahmed, Yunus; van den Brom, Charissa E; Bogaards, Sylvia; van Meurs, Matijs; Jongman, Rianne M; Schalkwijk, Casper G; Begieneman, Mark P V; Niessen, Hans W; Baufreton, Christophe; Boer, Christa

    2016-03-01

    Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.

  5. The Protective Role of Carnosic Acid against Beta-Amyloid Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    H. Rasoolijazi

    2013-01-01

    Full Text Available Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer’s disease (AD. Previous studies have demonstrated the role of carnosic acid (CA, an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protects against memory deficit caused by beta-amyloid toxicity in rats. Beta-amyloid (1–40 was injected by stereotaxic surgery into the Ca1 region of the hippocampus of rats in the Amyloid beta (Aβ groups. CA was delivered intraperitoneally, before and after surgery in animals in the CA groups. Passive avoidance learning and spontaneous alternation behavior were evaluated using the shuttle box and the Y-maze, respectively. The degenerating hippocampal neurons were detected by fluoro-jade b staining. We observed that beta-amyloid (1–40 can induce neurodegeneration in the Ca1 region of the hippocampus by using fluoro-jade b staining. Also, the behavioral tests revealed that CA may recover the passive avoidance learning and spontaneous alternation behavior scores in the Aβ + CA group, in comparison with the Aβ group. We found that CA may ameliorate the spatial and learning memory deficits induced by the toxicity of beta-amyloid in the rat hippocampus.

  6. Antiapoptotic and neuroprotective role of Curcumin in Pentylenetetrazole (PTZ) induced kindling model in rat.

    Science.gov (United States)

    Saha, Lekha; Chakrabarti, Amitava; Kumari, Sweta; Bhatia, Alka; Banerjee, Dibyojyoti

    2016-02-01

    Kindling, a sub threshold chemical or electrical stimulation, increases seizure duration and enhances accompanied behavior until it reaches a sort of equilibrium state. The present study aimed to explore the effect of curcumin on the development of kindling in PTZ kindled rats and its role in apoptosis and neuronal damage. In a PTZ kindled Wistar rat model, different doses of curcumin (100, 200 and 300 mg/kg) were administrated orally one hour before the PTZ injections on alternate day during the whole kindling days. The following parameters were compared between control and experimental groups: the course of kindling, stages of seizures, Histopathological scoring of hippocampus, antioxidant parameters in the hippocampus, DNA fragmentation and caspase-3 expression in hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer's Exact test were used for statistical analyses. PTZ, 30 mg/kg, induced kindling in rats after 32.0 ± 1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with curcumin in a dose-dependent manner. Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

  7. The role of glutathione detoxification pathway in MCLR-induced hepatotoxicity in SD rats.

    Science.gov (United States)

    Li, Shangchun; Chen, Jun; Xie, Ping; Guo, Xiaochun; Fan, Huihui; Yu, Dezhao; Zeng, Cheng; Chen, Liang

    2015-12-01

    In the present study, we investigated the role of glutathione (GSH) and its related enzymes in Sprague Dawley (SD) rats subjected to microcystin-leucine-arginine (MCLR)-induced hepatotoxicity. SD rats were intraperitoneally (i.p.) injected with MCLR after pretreating with or without buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH synthesis. The depletion of GSH with BSO enhanced MCLR-induced oxidative stress, resulting in more severe liver damage and higher MCLR accumulation. Similarly, the contents of malondialdehyde (MDA), total GSH (T-GSH), oxidized GSH (GSSG) and GSH were significantly enhanced in BSO pretreated rats following MCLR treatment. The study showed that the transcription of GSH-related enzymes such as glutathione-S-transferase (GST), γ-glutamylcysteine synthetase (γ-GCS), glutathione reductase (GR) varied in different ways (expect for glutathione peroxidase (GPx), whose gene expression was induced in all treated groups) with or without BSO pretreatment before MCLR exposure, suggesting an adaptative response of GSH-related enzymes at transcription level to combat enhancement of oxidative stress induced by MCLR when pretreated with BSO. These data suggested the tissues with low GSH concentration are highly vulnerable to MCLR toxicity and GSH was critical for the detoxification in MCLR-induced hepatotoxicity in vivo.

  8. The role of neurotensin in positive reinforcement in the rat central nucleus of amygdala.

    Science.gov (United States)

    László, Kristóf; Tóth, Krisztián; Kertes, Erika; Péczely, László; Lénárd, László

    2010-04-02

    In the central nervous system neurotensin (NT) acts as a neurotransmitter and neuromodulator. It was shown that NT has positive reinforcing effects after its direct microinjection into the ventral tegmental area. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, regulation of feeding, anxiety and emotional behavior. By means of immunohistochemical and radioimmune methods it was shown that the amygdaloid body is relatively rich in NT immunoreactive elements and NT receptors. The aim of our study was to examine the possible effects of NT on reinforcement and anxiety in the CeA. In conditioned place preference test male Wistar rats were microinjected bilaterally with 100 or 250 ng NT in volume of 0.4 microl or 35 ng neurotensin receptor 1 (NTS1) antagonist SR 48692 alone, or NTS1 antagonist 15 min before 100 ng NT treatment. Hundred or 250 ng NT significantly increased the time rats spent in the treatment quadrant. Prior treatment with the non-peptide NTS1 antagonist blocked the effects of NT. Antagonist itself did not influence the reinforcing effect. In elevated plus maze test we did not find differences among the groups as far as the anxiety index (time spent on the open arms) was concerned. Our results suggest that in the rat ACE NT has positive reinforcing effects. We clarified that NTS1s are involved in this action. It was also shown that NT does not influence anxiety behavior.

  9. Role of TGF-β1 in the Formation of Ovarian Interstitial Fibrosis in PCOS Rat

    Institute of Scientific and Technical Information of China (English)

    Zhu-lin MIAO; Zu-neng WANG; Yan-dong YANG; Long-qiu CHEN; Rong CUI; Xiao-lan WANG; Ru-qiang OU

    2008-01-01

    Objective To study the role of TGF-β1 in the formation of interstitial fibrosis and capsular thickening in the PCOS rats.Methods PCOS rat model were established by subcutaneous injection DHEA.Estradiol(E2).testosterone(T).follicular stimulating hormone(FSH).Iuteinizing hormone(LH).LH/FSH and fasting insulin(FINS)hormone values of the model were tested by microparticle enzyme immunoassay,the pathohistology of PCOS rat ovaries was observed by HE staining,and their ultrastructure was tested by transmission electron microscope(TEM).The expressions of TGF-β1 in PCOS group(n=20),and control group(n=20)were detected and evaluated by immunohistochemistry and image analysis system.Results The results of serum E2,T,LH/FSH,FINS,the ovarian pathological-histology and the ultrastructure showed that the model was esmblished successfully.Compared with control group:there was no significant difference of TGF-β1,expression intensity in oocytes,granulosa cells of the different developing stages of follicle in PCOS(P>0.05).But it was markedly higher expressed in the theca cells of antral follicles(P<0.01).and stromal cells(P<0.05)in PCOS group than in control group.Conclusion The abnormal expression of TGF-β1 in PCOS is the main cause of capsular thickening and interstitial fibrosis.TGF-β1 also takes part in regulating PCOS follicle development and atresia.

  10. A novel rat model to study the role of intracranial pressure modulation on optic neuropathies.

    Directory of Open Access Journals (Sweden)

    Uttio Roy Chowdhury

    Full Text Available Reduced intracranial pressure is considered a risk factor for glaucomatous optic neuropathies. All current data supporting intracranial pressure as a glaucoma risk factor comes from retrospective and prospective studies. Unfortunately, there are no relevant animal models for investigating this link experimentally. Here we report a novel rat model that can be used to study the role of intracranial pressure modulation on optic neuropathies. Stainless steel cannulae were inserted into the cisterna magna or the lateral ventricle of Sprague-Dawley and Brown Norway rats. The cannula was attached to a pressure transducer connected to a computer that recorded intracranial pressure in real-time. Intracranial pressure was modulated manually by adjusting the height of a column filled with artificial cerebrospinal fluid in relation to the animal's head. After data collection the morphological appearance of the brain tissue was analyzed. Based on ease of surgery and ability to retain the cannula, Brown Norway rats with the cannula implanted in the lateral ventricle were selected for further studies. Baseline intracranial pressure for rats was 5.5 ± 1.5 cm water (n=5. Lowering of the artificial cerebrospinal fluid column by 2 cm and 4 cm below head level reduced ICP to 3.7 ± 1.0 cm water (n=5 and 1.5 ± 0.6 cm water (n=4, a reduction of 33.0% and 72.7% below baseline. Raising the cerebrospinal fluid column by 4 cm increased ICP to 7.5 ± 1.4 cm water (n=2 corresponding to a 38.3% increase in intracranial pressure. Histological studies confirmed correct cannula placement and indicated minimal invasive damage to brain tissues. Our data suggests that the intraventricular cannula model is a unique and viable model that can be used to study the effect of altered intracranial pressure on glaucomatous optic neuropathies.

  11. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

    Directory of Open Access Journals (Sweden)

    J.B. Graceli

    2013-07-01

    Full Text Available The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc and progesterone (OVP, 1.7 mg·kg-1·day-1, sc. We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g. Furthermore, combining OVX + D (OD: 111.9±25.4 decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.

  12. Role of aqueous extract of Azadirachta indica leaves in an experimental model of Alzheimer's disease in rats

    OpenAIRE

    2013-01-01

    Background: Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by multiple cognitive deficits, is often accompanied by behavioral disorders and mood changes. Because of the non-availability of proper curative/preventive therapy for AD, the present study was designed to evaluate the possible role of Azadirachta indica in experimental AD in rats. Materials and Methods: Experimental AD in rats was produced by nucleus basalis magnacellularis lesion with ibotenic acid...

  13. Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats: a study in naturally occurring CCK-A receptor gene knockout rats.

    Science.gov (United States)

    Miyasaka, K; Suzuki, S; Kanai, S; Masuda, M; Funakoshi, A

    1999-10-01

    Whether cholecystokinin (CCK) has a direct action on duct cells and the role of CCK-A receptor in bicarbonate secretion were examined by comparing the results obtained from OLETF (CCK-A receptor-deficient rats) and control (LETO) rats. Rats were prepared with cannulae for draining bile and pancreatic juice separately, with two duodenal cannulae and an external jugular vein cannula. The experiments were conducted without anesthesia. The responses of bicarbonate secretion to intravenous infusion of CCK, acetyl-beta-methylcholine (Ach), and 2-deoxy-D-glucose (2DG), and to intraduodenal infusion of HCl and a liquid meal were examined. To examine the synergistic effect between CCK and secretin, the effect of CCK during a background secretin infusion was examined in LETO rats. CCK did not stimulate bicarbonate secretion in either strain, nor in LETO rats with secretin infusion. When gastric acid secretion was prevented by administration of omeprazole, Ach did not increase bicarbonate secretion, but 2DG did in both strains. Intraduodenal infusion of HCI and a liquid meal significantly increased bicarbonate secretion in both strains; however, the responses were much less in OLETF than LETO rats. In conclusion, intravenous injection of CCK did not stimulate bicarbonate secretion, and the lack of CCK-A receptor decreased bicarbonate secretion in response to luminal stimulants.

  14. Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

    Science.gov (United States)

    O'Brien, S F; Russell, J C; Dolphin, P J; Davidge, S T

    2000-08-01

    Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

  15. Role of ATP-sensitive potassium channels in modulating nociception in rat model of bone cancer pain.

    Science.gov (United States)

    Xia, Hui; Zhang, Dengwen; Yang, Shijie; Wang, Yu; Xu, Lin; Wu, Jinjing; Ren, Jing; Yao, Wenlong; Fan, Longchang; Zhang, Chuanhan; Tian, Yuke; Pan, Hui-Lin; Wang, Xueren

    2014-03-20

    Bone cancer pain is a major clinical problem and remains difficult to treat. ATP-sensitive potassium (KATP) channels may be involved in regulating nociceptive transmission at the spinal cord level. We determined the role of spinal KATP channels in the control of mechanical hypersensitivity in a rat model of bone cancer pain. The rat model of bone cancer pain was induced by implanting rat mammary gland carcinoma cells (Walker256) into the tibias. KATP modulators (pinacidil and glibenclamide) or the specific Kir6.2-siRNA were injected via an intrathecal catheter. The mechanical withdrawal threshold of rats was tested using von Frey filaments. The Kir6.2 mRNA and protein levels were measured by quantitative PCR and western blots, respectively. Intrathecal injection of pinacidil, a KATP channel opener, significantly increased the tactile withdrawal threshold of cancer cell-injected rats in a dose-dependent manner. In contrast, intrathecal delivery of glibenclamide, a KATP channel blocker, or the specific Kir6.2-siRNA significantly reduced the tactile withdrawal threshold of cancer cell-injected rats. The mRNA and protein levels of Kir6.2 in the spinal cord of cancer cell-injected rats were significantly lower than those in control rats. Our findings suggest that the KATP channel expression level in the spinal cord is reduced in bone cancer pain. Activation of KATP channels at the spinal level reduces pain hypersensitivity associated with bone cancer pain.

  16. Role of Nuclear Transcription Factor-KB in Endotoxin-induced Shock in Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxinshock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6h after LPS injection, the activation of NF-κB in blood mononuclear cells and the content of TNF-α and IL-6 in plasma was detected by enzyme-linked immunoadsordent assay (ELISA). The level of mean arterial pressure (MAP) and the histopathological changes of lung and liver were also observed. The activation of NF-κB in mononuclear cells increased 1 h after LPS injection and reached its peak 2 h after the injection, and its level was higher than that of normal group. The level of TNF-α was increased 1 h after the infusion and peaked 2 h after the injection, and its level was higher than that of normal group after LPS infusion. The content of IL-6 increased gradually with time, the IL-6 level was higher than that of normal group after LPS injection. MAP was decreased gradually with time and its level was lower than that of normal group after LPS injection. Pathological examination showed that endotoxic shock could cause pulmonary alveolar hemorrhage, edema and infiltration of inflammatory cell in lung tissue and congestion, edema, capillary dilation and inflammatory cell infiltration in liver tissue. It is concluded that NF-κB can up-regulate the expression of TNF-α and IL-6 in plasma and play an important role in endotoxin-induced shock in rats.

  17. ROLE OF CASPASE-3 IN ACUTE LIGHT DAMAGE TO RETINA OF RATS

    Institute of Scientific and Technical Information of China (English)

    Xiao Wang; Shi-xing Hu; Wei Li; Shao-chun Lin

    2007-01-01

    Objective To investigate the role of Caspase-3 in retinal damage caused by light exposure in rats.Methods Light injury to retina was induced by persistent exposure to illumination (intensity; 30000±50 lux) of operating microscope for 30 minutes in the right eyes of Sprague-Dawley rats. The pathological changes of retina were observed under optical and electron microscopies at different time points, which were 6 hours, 1,3,7,and 15 days after the light exposure. Apoptosis of retinal cells was analyzed by flow cytometry. The activity of Caspase-3 was evaluated by using the Caspase-3 assay kit. At the same time, the expression of Caspase-3 protease was determined with Western blot analysis.Results The examination results of optical and transmission electron microscopes showed that edema of inner and outer segments of the retina, espectially the chondriosome inside the inner segment, became obvious 6 hours after the light exposure. The change was deteriorated along with the increasing time. The structures of the discoidal valve dissociated in the outer segment simultaneously. Disorderly arranged nuclei, karyopycnosis, and thinning in the outer nuclear layer were observed. The retinal pogment epithelium almost disappeared during the later stage. The staining results of Annexin-V combined with PI demonstrated that the proportion of apoptotic cells increased with time. The proportion between 7th day (82.7%) and 15th day (80.4%), however, showed no significant difference. Caspase-3 became remarkably active with the lapse of time, which increased from 0.02 at 6th hour to the peak of 9.8 at 7th day before it started to descend. The Western blot detected a expression of the active form of Caspase-3 at 7th day and 15th day.Conclusion Apoptosis of photoreceptor cells is markedly involved in the light damage and Caspase-3 protease may play an important role in the apoptotic process of the retina after light exposure in rats.

  18. ROLE OF ENDOGENOUS CARBON MONOXIDE IN NEOINTIMAL FORMATION INDUCED BY BALLOON-INJURY IN RAT AORTA

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective.The present study investigated the role of endogenous carbon monoxide(CO)in the pathogenesis of neointimal formation induced by balloon injury in rat.Method.Endothelial denudation of the left common carotid artery of rat was carried out by three passages of a Fogarty 2F balloon catheter.DNA,collagen and elastin contents of each intima-media were estimated;and heme oxygenase(HO)activity and CO production in vascular smooth muscle cell(VSMC)were measured after administration of HO inhibitor.Result.Our data showed that neointima occurred in the rat on day 7 and day 21 after balloon injury,and at the same time HO activity and CO production in VSMC were markedly increased.Administration of HO inhibitor,zinc deuteroporphyrin 2,4-bisglycol(ZnDPBG),could effectively inhibit HO activity and CO production,significantly enhance neointimal formation(aortic intima/media ratio were 21.4±1.8% vs 17.6±2.0%,P<0.05 on day 7;and 30.5±2.4% vs 23.0±2.2%,P<0.01 on day 21,respectively,compared with balloon alone group).Conclusion.We concluded that 1)inhibition of CO production may enhance neointimal formation induced by endothelial denudation,implying endogenous CO play an protective role in response to vascular injury,and 2)induction of HO activity may be applied clinically for preventing restenosis after angioplasty.

  19. ROLE OF CALCINEURIN IN ANGIOTENSIN II INDUCED CARDIAC MYOCYTE HYPERTROPHY OF RATS

    Institute of Scientific and Technical Information of China (English)

    符民桂; 张继峰; 许松; 庞永政; 刘乃奎; 唐朝枢

    2001-01-01

    Objective. The present study investigated the role of calcineurin in angiotensin II(AngII) induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H leucine incorporation; atrial natriuretic factor(ANF) Mrna level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13% ,57% (P< 0.05) and 228% (P< 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H leucine incorporation in AngII treated cardiomyocytes in a dose dependent manner. It was also found that CsA slightly reduced the Mrna level of ANF gene in AngII stimulated cardiomyocytes. Conclusion. During AngII induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII induced myocardial hypertrophy of rats.

  20. The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat.

    Science.gov (United States)

    Baldi, Elisabetta; Mariottini, Chiara; Bucherelli, Corrado

    2007-12-01

    The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories.

  1. Invasive or non invasive angiography? The role of conventional catheder angiography; Invasive oder nichtinvasive Angiographie? Die Rolle der ``klassischen`` Katheter-Angiographie

    Energy Technology Data Exchange (ETDEWEB)

    Hagen, B. [Martin-Luther-Krankenhaus, Berlin (Germany). Radiologische Abt.

    1997-07-01

    Within the last decade, diagnostic and interventional angiography have been developed to a high degree of performance, due to the widespread use of DSA, the miniaturisation of the puncture trauma and the introduction sets (catheters, sheaths), the development of high-tech materials (e.g., Nitinol guidewires) and the application of non-ionic, low osmolal contrast media. The specific risks of the procedure, thereby, have been significantly reduced, but could not be totally eliminated. To evaluate vascular diseases non-invasively, special attention was attributed to the progress of colour coded duplex, (spiral) CT-angiography and (CE)MR-angiography, based on the estbalished imaging with US, CT and MRT. The matter in question is whether or not they can substitute the role of conventional angiography as the `gold standard` of vessel imaging. Clinical validity and economic efficiency both determine the indication for the use of invasive or non-invasive methods. In diagnostic procedures, there is a growing tendency for the use of non-invasive techniques, like in imaging of the abdominal and thoracic aorta, the renal, pulmonary and extra- and intra-cranial arteries. Conventional angiography is still reserved for the evaluation of small vessels of the upper and lower extremities, and vessel status in preoperative conditions (carotid, celiac trunk, mesenteric and renal arteries and aneurysms of the cerebral vasculature). Fluoroscopic guiding of catheters and contrast enhancement in interventional procedures, however, cannot be substituted by alternative techniques in the foreseeable future. (orig.) [Deutsch] Diagnostische und therapiebezogene Angiographietechniken haben in den letzten Jahren durch die fast ausschliessliche Anwendung der DSA, durch Miniaturisierung des Punktionstraumas und der Einfuehrungsbestecke (Katheter, Schleusen), durch Entwicklung von High-tech-Materialien (z.B. Nitinolfuehrungsdraehte) und Verwendung nichtionischer, niederosmolaler Kontrastmittel

  2. Evidence of altered histone interactions, as investigated by removal of histones, in chromatin isolated from rat liver nuclei by a conventional method.

    Science.gov (United States)

    Fenske, H; Eichhorn, I; Böttger, M; Lindigkeit, R

    1975-10-01

    It is shown that the release of the slightly lysine-rich histones f2a2 and f2b by 0.4 M ammonium sulfate from conventionally isolated chromatin is diminished in comparison to the lysed nuclei. The change in extractability is further demonstrated by the application of ethidium bromide. At a molar input ratio of 0.09 (moles ethidium bromide/moles nucleotide) and 0.4 M ammonium sulfate the slightly lysine-rich histones are released from the chromatin to 70 - 80% if the lysed nuclei are used. At 0.1 M ammonium sulfate ethidium bromide effected also a release of 50 % of histone f1. Comparable effects could not be observed with chromatin prepared in a conventional way but instead a tendency towards loss of histone f3 in the presence of ethidium bromide was observed.

  3. The Role of Nitric Oxide in Hyperoxic Lung Injury in Premature Rats

    Institute of Scientific and Technical Information of China (English)

    常立文; 马丽亚; 张晓慧; 陈晔

    2001-01-01

    To investigate the role of nitric oxide (NO) in hyperoxic lung injury, the 3-day-old preterm rats were randomly assigned to four groups: group I (hyperoxia group), group Ⅱ (hyperoxia+Nw-nitro-L-arginine methyl ester (L-NAME) group), group Ⅲ (air group), and group Ⅳ (air+L-NAME) group. Group Ⅰ and Ⅱ were exposed to ≥90 % O2 for 3 or 7 days. Group Ⅱ and Ⅳ received subcutaneous L-NAMEy on daily basis (20 mg/kg). After 3 day or 7 day exposure, the lung wet weight/dry weight ratio (W/D), total protein and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung pathology were examined in all groups. NO content, expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in lungs were measured in group Ⅰ and Ⅲ. Our results showed that after 3 day exposure, group Ⅰ appeared acute lung injury characterized by the increase of MDA content (P<0.01) and the presence of hyperaemia, red cell extravasation and inflammatory infiltration; after 7 day exposure, except MDA, total protein and W/D were also increased in comparison with group Ⅲ (P<0.01, 0.05), pathological changes were more severe than those after 3 day exposure. After 3 and 7 day exposure, total protein in group Ⅱ was significantly increased as compared with group Ⅰ (P<0.01 for both). The pulmonary acute inflammatory changes were more obvious in group Ⅱ than in group Ⅰ. Occasionally, mild hemorrhage was detected in the lungs of group Ⅳ. BALF protein content in group IV was higher than that in group Ⅲ after 7 day exposure (P<0.01). After 3 and 7 day exposure, NO content in BALF were all significantly elevated in group Ⅰ as compared with group Ⅲ (P<0.01 for all). In the lungs of group Ⅰ, strong immunostaining for iNOS was observed in airway and alveolar epithelia, inflammatory cells, which were stronger than those in group Ⅲ. Expression of iNOS in rats after 7 day hyperoxic exposure was stronger than that after 3 day exposure. Shortly after 7 day exposure

  4. Expression changes and roles of matrix metalloproteinases in a rat model of traumatic deep vein thrombosis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-bing; LI Wen; YAO Li-qing; ZHAO Xue-ling; WANG Bing; LI Hong-kun; NING Ya; SONG En; ZHANG Xin-xin

    2010-01-01

    Objective:To study the expression changes of matrix metal loproteinases (MMPs) in traumatic deep vein thrombosis (TDVT) in a rat model with the aid of gene chip technology and to explore the roles of MMPs in TDVT.Methods:Totally 150 Sprague Dawley rats were randomly divided into control group (n=10) and model group (n=140). Rat models of TDVT were established by clamping the femoral vein and fixing the bilateral hind limbs. Then fixation of the hip spica with plaster bandage was conducted.According to the observation phases and/or biological situations of the femoral vein thrombosis, the model rats were further divided into 7 groups. Vascular tissues were obtained from each group through noninvasive incision into the femoral vein at corresponding time points. We adopted the Trizoi one-step method for total RNA extraction,Affymetrix RAT 230 2.0 array for detection of RNA expressions and fold change (FC) analysis for changes of differential expressions of MMPs in each group. The main outcome parameters measured included expressions of MMP-2,MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11,MMP- 12, MMP-13, MMP- 14, MMP- 16, MMP-23 and MMP-24. Gene array data of these MMPs were analyzed by the Affymetrix Microarray Analysis software (Version 5.0).Results:FC analysis showed differential expressions of MMPs in each group during the course of TDVT. At the initial period of thrombosis, MMP-2, MMP-3, MMP-7,MMP-8, MMP-9, MMP- 10, MMP-11, and MMP-24 had significantly high expression, while MMP-12, MMP-13,MMP-14, MMP-16 and MMP-23 had relatively low expression. MMPs were all highly expressed at the peak time of thrombosis. In the process of thrombus resolution,MMP-2, MMP-10, MMP-16 and MMP-24 have relatively low expression, while MMP-12, MMP-13, MMP-14,MMP-16 and MMP-23 have significantly high expression.Conclusion:MMPs may affect the process of TDVT through transcription regulation of the fibrinolysis-anti-fibrinolytic system during the course of thrombosis and thrombus resolution.

  5. Role of sensory nerves in gastroprotective effect of anandamide in rats.

    Science.gov (United States)

    Warzecha, Z; Dembinski, A; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Kownacki, P; Konturek, P C

    2011-04-01

    Previous studies have shown that stimulation of cannabinoid 1 (CB1) receptor protects the gastric mucosa against stress-induced lesion. Aim of the present study was to examine the influence of anandamide on lipid peroxidation and antioxidant defense system in gastric mucosa and the role of sensory nerves in gastroprotective effects of cannabinoids. Studies were performed on rats with intact or ablated sensory nerves (by neurotoxic doses of capsaicin). Gastric lesions were induced by water immersion and restrain stress (WRS). Anandamide was administered at the dose of 0.3, 1.5 or 3.0 μmol/kg, 30 min before exposure to WRS. CB1 receptor antagonist, AM251 (4.0 μmol/kg) was administered 40 min before WRS. WRS induced gastric lesions associated with the decrease in gastric blood flow, mucosal DNA synthesis and mucosal activity of superoxide dismutase (SOD). Serum level of interleukin-1β (IL-1β) and mucosal level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were increased. Administration of anandamide reduced the ulcers area, generation of MDA+4-HNE and serum level of IL-1β, and this effect was associated with the reduction in the WRS-induced decrease in gastric mucosal blood flow, mucosal DNA synthesis and SOD activity. Ablation of sensory nerves increased the area of ulcers, serum level of IL-1β and mucosal content of MDA+4-HNE, whereas mucosal DNA synthesis, SOD activity and blood flow were additionally decreased. In rats with ablation of sensory nerves, administration of anandamide at the high doses (1.5 and 3.0 μmol/kg) partly reduced deleterious effect of WRS on gastric mucosa, but this effect was weaker than in animals with intact sensory nerves. Low dose of anandamide (0.3 μmol/kg) was ineffective in the protection of gastric mucosa against the WRS-induced lesions in rats with ablation of sensory nerves. In rats with intact sensory nerves and exposed to WRS, administration of AM251 exhibited deleterious effect. In rats with ablation of sensory

  6. AN EXPERIMENTAL COMPARATIVE STUDY OF ANALGESIC ACTIVITY OF CURCUMA: AMADA (MANGO - GINGER WITH CONVENTIONAL NSAID ASPIRIN IN MALE ALBINO WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Shanmukananda

    2015-09-01

    Full Text Available BACKGROUND: Mango ginger ( Curcuma amada Roxb. belongs to Zingiberaceae family has biological activities include antioxidant, antibacterial, antifungal, anti - inflammatory, antiallergic, CNS depressant and analgesic activity. The major chemical components include starch, phenolic acids, volatile oils, curcuminoids and terpenoids like difurocumenonol, amadannulen and amadaldehyde. Pain is often the first indication of disease or injury and a major symptom in many clinical conditions and can significantly interferes with a person’s quality of life and general functioning. The standard and test drugs suppress the inflammatory mediators associated with pain. This article brings out the analgesic activity of C. Amada in comparison with aspirin. Therefore aqueous extract of C. amada was evaluated for analgesic activity in animal models of pain. OBJECTIVES: 1. To evaluate rhizomes of Curcuma Amada for analgesic activity in male albino wistar rats and to compare the analgesic activity with aspirin . 2. To Evaluate if combination of Curcuma Amada with aspirin is synergistic . MATERIALS AND METHODS: Albino rats are the proven models for analgesic studies. They were obtained from the animal house of DR.B. R. Ambedkar Medical College. Animals were maintained as per CPCSEA guidelines .The aqueous extract of Curcuma Amada was used. Aspirin (100mg/kg was used as the standard analgesic drug. 4x4 groups of 6 Rats were used to ensure that results obtained were statistically significant using ANOVA test. Analgesic activity will be assessed with the help of following screening methods Acetic Acid Writhing Method using Acetic Acid, Tail Flick Method using the Analgesiometer, Tail Immersion Method using Hot Water (55 0 C , Hot Plate method using Hot Plate . RESULTS : Aqueous extract of Curcuma Amada significantly suppressed the 1% acetic acid induced writhing response in rats when compared to standard drug aspirin. In the Tail flick and Hot plate test Curcuma

  7. Role and outcome of conventional surgery in the treatment of pyogenic liver abscess in the modern era of minimally invasive therapy

    Institute of Scientific and Technical Information of China (English)

    Simon Siu-Man Ng; Janet Fung-Yee Lee; Paul Bo-San Lai

    2008-01-01

    AIM:To evaluate the role and outcome of conventional surgery in the treatment of pyogenic liver abscess in the modern era of minimally invasive therapy.METHODS:The medical records of thirteen patients with pyogenic liver abscess who underwent surgical treatment between January 1995 and December 2002 were retrospectively reviewed to determine the clinical presentation,indication and nature of surgery,and out-come of surgery.RESULTS:The patients were predominantly women (10/13) with a mean age of 65±17 years.Their main presenting symptoms were abdominal pain (100%) and fever (77%).The aetiologies included biliary (n = 6),cryptogenic (n = 3),portal (n = 2),and trauma (n = 2).Seven patients underwent percutaneous drainage as the initial treatment.Of these,three patients developed peritonitis secondary to peritoneal spillage.Another four patients failed to respond because of multilocula-tion.Salvage surgery was required in these patients.Six patients proceeded to straight laparotomy:two had marked sepsis and multiloculated abscess that precluded percutaneous drainage,and four presented with perito-nitis of uncertain pathology.Surgical procedures included deroofment and drainage (n = 9),liver resection (n = 3),peritoneal lavage (n = 2),cholecystectomy (n = 4),and exploration of common bile duct (n = 2).One patient required reoperation because of bleeding.Three patients required further percutaneous drainage after surgery.The overall mortality was 46%.Four patients died of multiorgan failure and two patients died of pulmonary embolism.CONCLUSION:Surgical treatment of pyogenic liver ab-scess is occasionally needed when percutaneous drain-age has failed due to various reasons.Mortality rate in this group of patients has remained high.

  8. Protective Role of Sodium Selenite on Mercuric Chloride Induced Oxidative and Renal Stress in Rats

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    Necib, Youcef

    2013-04-01

    Full Text Available Backgroud: Reactive oxygen species are known to play a major role in mercuric chloride induced oxidative and renal stress. Sodium selenite as an exogenous source of selenium is used for endogenous selenoprotein synthesis to scavenge the free radicals. The study was designed to investigate the possible protective role of sodium selenite in mercuric chloride induced renal stress, by using biochemical approaches. Adult male Albinos Wistar rats were randomly divided into four groups. The first group was served as the control, the second group was given sodium selenite (0.25 mg/kg b.w, while the third group was given mercuric chloride (0.25 mg/kg, finally, the fourth group was given combined treatment of sodium selenite and mercuric chloride for 3 weeks.Results: The effects of sodium selenite on mercuric chloride induced oxidative and renal stress were evaluated by serum creatinine, urea, uric acid, billirubin levels and LDH activity, kidney tissue lipid peroxidation, GSH levels, GSH-Px, GST and catalase activities and hematological parameters. Administration of mercuric chloride induced significant increase in serum: creatinine, urea, uric acid and billirubin concentration showing renal stress. Mercuric chloride also induced oxidative stress, as indicate by decreased kidney tissue of GSH level, GSH-Px, GST, and catalase activities along with increase the level of lipid peroxidation. Furthermore, treatment with mercuric chloride caused a marked elevation of kidney weight and decreased body weight and erythrocytes, hemoglobin, hematocrit levels. Sodium selenite treatment markedly reduced elevated serum: creatinine, urea, uric acid and billirubin levels, and LDH activity and conteracted the deterious effects of mercuric chloride on oxidative stress markers and hematological parameters and atteneuated histopathological changes caused by HgCl2 in kidney.Conclusion: Our results indicate that sodium selenite could have a beneficial role against mercuric

  9. The critical role of leukotriene B4 in antigen-induced mechanical hyperalgesia in immunised rats

    Science.gov (United States)

    Cunha, Joice Maria; Sachs, Daniela; Canetti, Claudio Azevedo; Poole, Stephen; Ferreira, Sérgio Henrique; Cunha, Fernando Queiroz

    2003-01-01

    We investigated the mediators responsible for mechanical hypersensitivity induced by antigen challenge in rats immunised with ovalbumin (OVA). Challenge with OVA (12.5–100 μg, intraplantar) caused a dose- and time-dependent mechanical hypersensitivity, which peaked 3 h after, decreased thereafter and reached control levels 24 h later. Levels of TNFα, IL-1β and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were increased in paw skin after antigen challenge. OVA-evoked hypersensitivity was partially inhibited (about 51%) by pretreatment with anti-TNFα , IL-1β and IL-8 sera or with IL-1 receptor antagonist (IL-1ra), but not anti-NGF serum. Pretreatment with thalidomide (45 mg kg−1) or pentoxifylline (100 mg kg−1) also partially inhibited the hypersensitivity at 1–3 h after challenge. Pretreatment with indomethacin (5 mg kg−1) or atenolol (1 mg kg−1) reduced the OVA-induced hypersensitivity at 1 and 3 h, but not at 5 h after challenge, while the combination of B1 and B2 bradykinin receptor antagonists was ineffective over the same times. Pretreatment with MK886 (5-lipoxygenase-activating protein inhibitor, 3 mg kg−1), CP 105696 (LTB4 receptor antagonist; 3 mg kg−1) or dexamethasone (0.5 mg kg−1) inhibited the hypersensitivity from 1 to 5 h. Furthermore, LTB4 levels were increased in the paw skin of challenged rats. In conclusion, our results suggest that the TNFα-, IL-1β- and CINC-1-driven release of prostaglandins, sympathetic amines and LTB4 mediates the first 3 h of mechanical hypersensitivity induced by antigen challenge in rats. At 5 h after OVA administration, although TNFα has some role, LTB4 is the critical nociceptive mediator. PMID:12871832

  10. The role of transforming growth factor alpha in rat craniofacial development and chondrogenesis.

    Science.gov (United States)

    Huang, L; Solursh, M; Sandra, A

    1996-08-01

    To explore the possible role of transforming growth factor alpha (TGF-alpha) in craniofacial development, its expression in the craniofacial region of rat embryos from embryonic day (d) 9 to d 20 was examined by in situ hybridisation and immunostaining. The TGF-alpha transcripts were first detected in the neural fold of embryonic d 9 and 10 embryos. In the craniofacial region, the TGF-alpha transcripts were not detected until embryonic d 16 in mesenchyme surrounding the olfactory bulb, within the olfactory bulb, the nasal capsule, vomeronasal organ, and vibrissal follicle. In addition, TGF-alpha message was detected in mesenchyme in the vicinity of Meckel's cartilage, and in the dental epithelium and lamina. This expression pattern of TGF-alpha transcripts persisted until embryonic d 17 but disappeared by d 18. The presence of TGF-alpha protein largely coincided with TGF-alpha message although, unlike the message, it persisted throughout later embryogenesis in the craniofacial region. The possible function of TGF-alpha in chondrogenesis was explored by employing the micromass culture technique. Cartilage nodule formation in mesenchymal cells cultured from rat mandibles in the presence of TGF-alpha was significantly inhibited. This inhibitory effect of TGF-alpha on chondrogenesis was reversed by addition of antibody against the EGF receptor, which crossreacts with the TGF-alpha receptor. The inhibitory effect of TGF-alpha on chondrogenesis in vitro was further confirmed by micromass culture using mesenchymal cells from rat embryonic limb bud. Taken together, these results demonstrate the involvement of TGF-alpha in chondrogenesis during embryonic development, possibly by way of a specific inhibition of cartilage formation from mesenchymal precursor cells.

  11. Protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats.

    Science.gov (United States)

    Koriem, Khaled M M; Fathi, Gamal E; Salem, Huda A; Akram, Nabil H; Gamil, Sofie A

    2013-05-01

    Cadmium has been classified as an environmental pollutant and human carcinogen. Pectin is a family of complex polysaccharides that function as hydrating agents and cementing materials for the cellulosic network. The aim of this study was to evaluate the protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Forty male Wistar rats were divided into five equal groups. Groups 1 and 2 were injected intraperitoneally (i.p.) saline (1 mg/kg) and pectin (50 mg/kg), respectively, two days/weeks over three weeks period. Groups 3-5 were injected i.p. with 1 mg/kg cadmium two days/week while groups 4 and 5 co-administrated i.p. with 25 and 50 mg/kg pectin, respectively, three days/week over three weeks period. The results of the present work revealed that cadmium-exposed rats showed decrease in serum testosterone, dehydroepiandrosterone sulfate and lactate dehydrogenase. Testicular cholesterol, total protein, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and reduced glutathione levels were also decreased while testicular malondialdehyde level was increased after cadmium injection. On the other hand, serum luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and γ-glutamyl transpeptidase were increased after cadmium exposure. Cadmium also induced sperms loss. Co-administration of pectin with cadmium restores all the above parameters and sperms to the normal levels where pectin at higher dose was more effective than lower one. These results were supported by histochemical investigations. In conclusion, pectin can counteract the testicular toxicity and oxidative stress induced by cadmium and the effect was dose-dependent.

  12. Protective role of L-carnitine supplementation against exhaustive exercise induced oxidative stress in rats.

    Science.gov (United States)

    Síktar, Elif; Ekinci, Deniz; Síktar, Erdinç; Beydemir, Sükrü; Gülçin, Ilhami; Günay, Mehmet

    2011-10-15

    The objective of this study was to investigate temperature dependent effects of oral l-carnitine supplementation on exhaustive exercise induced oxidative damage in rats. 42 male Spraque Dawley rats were randomly divided into seven experimental groups. These groups were formed as three non-carnitine exercise groups, three carnitine-exercise groups and a sedentary group. l-carnitine was given intraperitoneally to the carnitine-exercise groups 1h before the exercise in 100mg/kg. Blood was collected to measure paraoxonase-1 (PON1) activity, plasma malondialdehyde (MDA), low-density lipoprotein (LDL) and cholesterol concentrations. These biomarkers were measured in venous blood samples collected before and after the rats swam in pools at different water temperatures (18°C, 28°C and 38°C). In the non-carnitine group, exercise caused a significant decrease in PON1 activity and a significant elevation in MDA concentration at 28°C compared to the sedentary group. No significant alterations were evidenced in LDL and cholesterol concentrations upon exercise. The decrease in PON1 activity became higher with increasing temperature whereas the elevation in MDA levels increased at 18°C. In the l-carnitine supplementation group, recovery in PON1 activity was observed significant at 28°C and very significant at 38°C. MDA concentration was almost the same with that of the non-carnitine group at 18 and 38°C, but it significantly decreased at 28°C. Considering the recovery in PON1 and MDA levels at 28°C, which is the temperature of the sedentary group; our results suggest that l-carnitine supplementation has a protective role on exhaustive exercise-induced oxidative stress. Findings of this study also demonstrate influences of thermal stress on these parameters during exhaustive exercise.

  13. The role of NADPH oxidase in taurine attenuation of Streptococcus uberis-induced mastitis in rats.

    Science.gov (United States)

    Miao, Jinfeng; Zhang, Jinqiu; Ma, Zili; Zheng, Liuhai

    2013-08-01

    In order to evaluate the role of taurine on the oxidative stress mediated by NADPH oxidase in Streptococcus uberis-induced (S. uberis) mastitis, rats were administered daily (per os) 100mg/kg of taurine (group TS) or an equal volume of physiological saline (group CS) from gestation day 14 until parturition. Seventy-two hours after parturition, approximately 100cfu of S. uberis was infused into each of 2 mammary glands. Pretreatment with taurine significantly decreased mRNA and protein expression of p47phox and p22phox in mammary tissues. The total anti-oxidation capability (T-AOC) levels and superoxide dismutase (SOD) activities decreased, while malondialdehyde (MDA) levels increased both in mammary tissues and serum of rats with intramammary S. uberis infusion. Gavage administration of taurine moderated this change. Concentrations of interleukin-1β (IL-1β) and IL-6 in mammary glands decreased as a result of taurine administration. Significant differences (Ptaurine has the ability of regulating redox conditions which leads to the suppression of oxidative stress and secretion of proinflammatory cytokines. This phenomenon may be ascribed to taurines's ability to inhibit the expression of NADPH oxidase. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Role of the area postrema in three putative measures of motion sickness in the rat

    Science.gov (United States)

    Sutton, Richard L.; Fox, Robert A.; Daunton, Nancy G.

    1991-01-01

    After thermal cauterization of the area postrema in rats, the absence of conditioned taste aversion of sucrose paired with lithium chloride (0.15M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 deg/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.

  15. Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

    Directory of Open Access Journals (Sweden)

    Nouf Al-Rasheed

    2015-08-01

    Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

  16. Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor.

    Science.gov (United States)

    Calabrese, Francesca; Guidotti, Gianluigi; Racagni, Giorgio; Riva, Marco A

    2013-12-01

    Aging is a physiological process characterized by a significant reduction of neuronal plasticity that might contribute to the functional defects observed in old subjects. Even if the neurobiological mechanisms that contribute to such impairment remain largely unknown, a role for neurotrophic molecules, such as the neurotrophin brain-derived neurotrophic factor (BDNF), has been postulated. On this basis, the purpose of this study was to provide a detailed investigation of the BDNF system, at transcriptional and translational levels, in the ventral and dorsal hippocampus and in the prefrontal cortex of middle-aged and old rats, compared with in adult animals. The expression of major players in BDNF regulation and response, including the transcription factors, calcium-responsive transcription factor, cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB), and neuronal Per Arnt Sim (PAS) domain protein 4, and the high-affinity receptor tropomyosin receptor kinase B (TrkB), was also analyzed. Our results demonstrate that the BDNF system is affected at different levels in aged rats with global impairment including reduced transcription, impaired protein synthesis and processing, and decreased activation of the TrkB receptors. These modifications might contribute to the cognitive deficits associated with aging and suggest that pharmacological strategies aimed at restoring reduced neurotrophism might be useful to counteract age-related cognitive decline.

  17. Expression and role of PAK6 after spinal cord injury in adult rat

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    CHEN Xiang-dong

    2012-02-01

    Full Text Available 【Abstract】Objective: To observe p21-activated kinase 6 (PAK6 expression and its possible role after spinal cord injury (SCI in adult rat. Methods: Sprague-Dawley rats were subjected to spinal cord injury. To explore the pathological and physiological significance of PAK6, the expression patterns and distribution of PAK6 were observed by Western blot, immunohistochemistry and immunofluorescence. Results: Western blot analysis showed PAK6 protein level was significantly up-regulated on day 2 and day 4, then reduced and had no up-regulation till day 14. Immunohistochemistry analysis showed that the expression of PAK6 was significantly increased on day 4 compared with the control group. Besides, double immunofluorescence staining showed PAK6 was primarily expressed in the neurons and astrocytes in the control group. While after injury, the expression of PAK6 was increased significantly in the astrocytes and neurons, and the astrocytes were largely proliferated. We also examined the expression of proliferating cell nuclear antigen (PCNA and found its change was correlated with the expression of PAK6. Importantly, double immunofluorescence staining revealed that cell proliferation evaluated by PCNA appeared in many PAK6-expressing cells on day 4 after injury. Conclusion: The up-regulation of PAK6 in the injured spinal cord may be associated with glial proliferation. Key words: PAK6 protein, human; p21-activated kinases; Spinal cord injury; Astrocytes

  18. Ischemia and reperfusion injury of the rat liver: the role of nimodipine.

    Science.gov (United States)

    Chávez-Cartaya, R E; Pino DeSola, G; Ramirez-Romero, P; Calne, R Y; Jamieson, N V

    1996-01-01

    The protective effect of the calcium channel blocker nimodipine on liver ischemia and reperfusion was studied in the rat. The homeostasis of intracellular calcium ions seems to be a determinant factor in the cell injury that appears after ischemia and reperfusion. Nimodipine was used to downregulate the calcium levels in the cytosol of the ischemic cell, the hypothetical role of Ca2+ in the pathogenesis of ischemia and reperfusion injury. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver and subsequent reperfusion after a period of 45 min of ischemia. Nimodipine (10 micrograms/kg body wt) was administered either before or after the onset of ischemia. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using a He-Ne laser Doppler flowmeter and photometer, which showed, in the pretreated group, a recovery of reperfusion blood flow (58.1%) and liver reflectance (85.5%) significantly better (P flow (32.8%) and reflectance (70.5%). In the group that received nimodipine after ischemia, the recovery of the blood flow and the postreperfusion liver reflectance were not significantly better than those in the untreated control group. ALT levels (P < 0.05), galactose elimination capacity (P < 0.001), and histological studies also showed a protective effect of calcium antagonist nimodipine when administered before ischemia.

  19. Role of N-acetylcysteine in rifampicin-induced hepatic injury of young rats

    Institute of Scientific and Technical Information of China (English)

    SV Rana; S Attri; K Vaiphei; R Pal; A Attri; K Singh

    2006-01-01

    AIM: To study the role of N-acetylcysteine (NAC) as a protective agent in rifampicin (RMP)-induced oxidative hepatic injury of young rats.METHODS: Hepatic injury was produced by giving 50mg/kg body weight/day of RMP for 3 wk. A dose of NAC (100mg/kg body weight/day) was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations.RESULTS: RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol (GSH) status was well preserved. Cytochrome P4s0 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels.CONCLUSION: NAC protects young rats against RMP-induced oxidative hepatic injury.

  20. The role of visfatin on the regulation of inflammation and apoptosis in the spleen of LPS-treated rats.

    Science.gov (United States)

    Xiao, Ke; Zou, Wei-Hua; Yang, Zhi; Zia ur Rehman; Ansari, Abdur Rahman; Yuan, Huai-Rui; Zhou, Ying; Cui, Lu; Peng, Ke-Mei; Song, Hui

    2015-02-01

    The purpose of the present study is to determine if visfatin is involved in inflammation or apoptosis induced by LPS in rat. Forty Wistar rats were divided into four groups: saline group, LPS group, visfatin group and Visfatin + LPS co-stimulated group. Spleen samples from each group of rats were collected for study. The spleen structure was examined by histological imaging. Apoptosis was evaluated with TUNEL reaction. Caspase-3 was detected with immunohistochemistry and western blot. The apoptosis-related genes were detected by qPCR and inflammatory cytokines were tested by ELISA. Our main findings were as follows. (1) Macrophages were markedly increased in the visfatin group compared with the saline group. This finding was confirmed when spleen samples were examined with western blot using CD68 antibody. (2) Visfatin promoted the expression of CD68 and caspase-3 in rat spleen, whereas visfatin could inhibit the expression of CD68 and activated caspase-3 in spleen of LPS-induced acute inflammation. (3) Visfatin had a pro-apoptotic effect on normal rat spleen, whereas it exerted an anti-apoptotic effect during LPS-induced lymphocytes apoptosis in rat spleen. Moreover, the effect of visfatin on cell apoptosis was mediated by the mitochondrial pathway. (4) Visfatin could modulate both the anti-inflammatory cytokines and pro-inflammatory cytokines in rat spleen, such as IL-10, IL-4, IL-6, TNF-α and IL-1β. Taken together, we demonstrate that visfatin could participate in the inflammatory process in rat spleen by modulating the macrophages and inflammatory cytokines. Also, visfatin plays a dual role in the apoptosis in rat spleen, which is mediated by the mitochondrial pathway.

  1. Global EDGAR greenhouse gas emissions and national emissions reporting under the UN Climate Convention: availability, structure, definitions and role of uncertainties

    Science.gov (United States)

    Olivier, J. G.; Monni, S.; van Aardenne, J.; Doering, U. M.; Janssens-Maenhout, G.; Peters, J. A.; Pagliari, V.

    2010-12-01

    JRC and PBL have compiled a comprehensive EDGAR v4 dataset for the ‘six’ greenhouse gases included in the Kyoto Protocol (CO2, CH4, N2O, HFCs, PFCs and SF6), which were constructed using consistently the 2006 IPCC methodology and combining activity data (international statistics) from publicly available sources and for the first time - to the extent possible - emission factors as recommended by the IPCC 2006 guidelines for GHG emission inventories. This dataset, that covers all countries, provides independent estimates for all anthropogenic sources from 1970 onwards that are consistent over time and comparable between countries. By using high resolution global grid maps per source category, we also compiled datasets with annual emissions on a 0.1x0.1 degree grid, as input for atmospheric models. Of the 220 UN nations only 43 industrialised countries (‘Annex I’) annually report their national GHG emissions in large detail from 1990 up to (presently) 2008, while most developing countries (‘non-Annex I’) for the UN Climate Convention (UNFCCC) and the Kyoto Protocol only report a summary table with emissions for one or more years (many only for 1994). All emissions in EDGAR 4 are detailed at country level using the same standard IPCC inventory source categories as used by industrialised countries in their report to the Climate Convention. Thus we provide full and up-to-date inventories per country, also for developing countries that go beyond the mostly very aggregated UNFCCC reports of the developing countries. Moreover, the time series back in time to 1970 provides for the UNFCCC trends a historic perspective. As part of our objective to contribute to more reliable inventories by providing a reference emissions database for emission scenarios, inventory comparisons and for atmospheric modellers, we strive to transparently document all data sources used and assumptions made where data was missing, in particular for assumptions made on the shares of

  2. The role of NF-κB activation in lipopolysacchavide induced keratitis in rats

    Institute of Scientific and Technical Information of China (English)

    WU Xin-yi; HAN Shao-ping; REN Mei-yu; CHANG Yuan; YU Fu-xin

    2005-01-01

    Background Nuclear factor-kappa B (NF-κB) is elevated in regulating transcription of many cytokines and inflammatory mediators. The purpose of this study was to investigate the activation and the significance NF-κB in lipopolysaccharide (LPS) induced keratitis.Methods LPS induced keratitis model was based on Wistar rats. At 0.5, 1, 3, 6, 12, 24 or 72 hours after LPS treatment, the rat corneas were observed with a slit lamp microscope, then the rats were sacrificed and their corneas were excised for routine histological analysis. The expression of NF-κB was detected with immunohistochemical staining. The change of tumour necrosis factors-α (TNF-α) mRNA expression was identified by reverse transcriptase polymerase chain reaction (RT-PCR).Results Histological findings demonstrated that LPS treated corneas showed significant changes in corneal structure. Corneal edema, pronounced inflammatory cells infiltration and inordinate collagen fibres were observed. Immunohistochemical results showed that the expression of NF-κB and its activation obviously increased after LPS treatment compared with the normal group and control group. Positive cells could be observed at 0.5 hour and peak expression of NF-κB was observed between 3 hours and 12 hours after infection, but returned to or approached normal level by 72 hours. RT-PCR showed that the level of TNF-α mRNA began to increase 0.5 hour after LPS treatment, peaked at 6 hours and then subsided by 72 hours. NF-κB had a positive correlation with the expression of TNF-α mRNA (r=0.964, P<0.01), both NF-κB and TNF-α had a strong positive correlation with the degree of inflammatory response in LPS treated corneas (r=0.929, P<0.01; r=0.587, P<0.05, respectively).Conclusions The activation of NF-κB was increased in LPS treated corneas and was elevated in LPS induced keratitis by promoting overexpression of TNF-α mRNA. NF-κB may play an important role in the pathogenesis of LPS-associated keratitis in rats.

  3. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Graceli, J.B. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2013-07-02

    The maintenance of extracellular Na{sup +} and Cl{sup -} concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na{sup +} and Cl{sup -} reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg{sup -1}·day{sup -1}, sc) and progesterone (OVP, 1.7 mg·kg{sup -1}·day{sup -1}, sc). We assessed Na{sup +} and Cl{sup -} fractional excretion (FE{sub Na{sup {sub +}}} and FE{sub Cl{sup {sub -}}}, respectively) and renal and plasma catecholamine release concentrations. FE{sub Na{sup {sub +}}}, FE{sub Cl{sup {sub -}}}, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE{sub Na{sup {sub +}}}, FE{sub Cl{sup {sub -}}}, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen

  4. ROLE OF D2 DOPAMINE RECEPTOR ON MODULATION OF THE LEUKOCYTE FORMULA IN RESTRAINT STRESSED RATS

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2006-08-01

    Full Text Available Dopamine is a monoamine neurotransmitter of both central and peripheral nervous system. Its role in the neural-immune communication has been discussed in the present study. Results reveal that in vivo blockade of D2 dopamine receptor by means of sulpiride, a selective antagonist for D2 dopamine receptor produce changes in functional activities of the immune effector cells. Adults rats pretreated once with LPS (a bacterial product (25µg/250µl, i.p., produce an immune response, were subjected to i.p. injection with sulpiride (4 mg/kg b.w., i.p., a selective antagonist for D2 dopamine receptors, after 3 days postimmunization. After 18 days later, we assessed the total leukocyte number, neutrophils, eosinophils and basophils number. In summary, we provide that D2 dopamine receptor blockade suppress or enhance the immune effector cells number in restraint stress.

  5. Effect of restraint stress on nociceptive responses in rats: role of the histaminergic system.

    Science.gov (United States)

    Ibironke, G F; Mordi, N E

    2011-12-20

    Stress induced analgesia (SIA) is well known, but the reverse phenomenon, hyperalgesia is poorly documented. This study investigated the role of the histaminergic system in restraint stress hyperalgesia in rats, using thermal stimulation method (hot plate and tail flick tests). Paw licking and tail withdrawal latencies were taken before and after restraint for about one hour. Significant decreases (p<0.05) were obtained in these latencies after the restraint in both tests. Administration of H1 and H2 receptor blockers, chlorpheniramine and cimetidine respectively 30 mins before the restraint still resulted in significant reductions (p<0.05) in these latencies, connoting the persistence of hyperalgesia, showing that histamine H1 and H2 receptors did not participate in the mechanism of restraint stress hyperalgesia. We therefore suggest a histaminergic independent mechanism for restraint stress induced hyperalgesia.

  6. Possible role of ependymal proliferation in improving experimental allergic encephalomyelitis in Lewis rats.

    Science.gov (United States)

    Mohamed, Adel; Yunus, Mohammed; Hamadain, Elgenaid; Benghuzzi, H

    2006-01-01

    Experimental autoimmune encephalomyelitis (EAE) animal models is an autoimmune demyelinating disease of the central nervous system, which is widely accepted as an animal for human multiple sclerosis (MS). Ependymal cells line the spinal canal and cerebral ventricles and proliferate in response to damage. These cells have the potential to differentiate into neural support cells. However, there is controversy as whether the response of the ependymal cells is a result of injury or repair. This study demonstrates using the rat EAE model a proliferative response of the ependymal cells occurred as a result of the disease. Interestingly, a more pronounced ependymal proliferative effect was seen in animals being fed a phase 2 enzyme inducer. The data suggests ependymal cells play a role in the post-inflammatory response of the brain and also may be involved in the remyelination process.

  7. Role of newly formed platelets in thrombus formation in rat after clopidogrel treatment

    DEFF Research Database (Denmark)

    Kuijpers, Marijke J E; Megens, Remco T A; Nikookhesal, Elham

    2011-01-01

    Platelet P2Y₁₂ receptors play an important role in arterial thrombosis by stimulating thrombus growth. Both irreversibly (clopidogrel) and reversibly binding (ticagrelor, AZD6140) P2Y₁₂ antagonists are clinically used for restricted periods, but possible differences in platelet function recovery...... after drug cessation have not been investigated. We treated WKY rats with a single, high dose of 200 mg/kg clopidogrel or 40 mg/kg ticagrelor. Blood was collected at different time points after treatment. Flow cytometry confirmed full platelet protection against ADP-induced αIIbβ₃ activation shortly...... after clopidogrel or ticagrelor treatment. At later time points after clopidogrel treatment, a subpopulation of juvenile platelets appeared that was fully responsive to ADP. Addition of ticagrelor to clopidogrel-treated blood reduced αIIbβ₃ activation of the unprotected platelets. In contrast, at later...

  8. Role of Ocimum sanctum in the experimental model of Alzheimer′s disease in rats

    Directory of Open Access Journals (Sweden)

    Raghavendra M

    2009-01-01

    Full Text Available Alzheimer′s disease (AD, a neurodegenerative disorder incapacitating elderly people towards the end of their life, accounts for approximately 70% of dementia. It affects 17-25 million elderly people worldwide. In spite of the remarkable increase in scientific knowledge about the pathobiology of AD, attempts other than modifying the cholinergic neurotransmission have proved futile. In Ayurveda a number of agents are in use, since ancient times, for chronic debilitating disorders. One such preparation, Ocimum sanctum (OS has been found to possess anti-ulcerogenic, anti-inflammatory and neuroprotective activities. Because of the nonavailability of proper curative therapy for AD, the present study has been undertaken to evaluate the possible role of OS in experimental AD in rats. Experimental AD in rats was produced by a nucleus basalis magnacellularis lesion with ibotenic acid (IB and intracerebroventricular (i.c.v administration of colchicine (Col. Various behavioural tests and biochemical analysis were performed to explore the possible role of OS in AD. OS exhibited anxiolytic activity in an open field test. In an elevated plus maze test, OS significantly alleviated IB, and Col induced anxiety and depression in the Porsolt′s swim test. In Morris′ water maze test, OS pretreatments improved reference memory, working memory and spatial learning. Both IB and Col induced deficits in active avoidance learning and retention of learned behaviour, which were significantly reversed by OS. IB and Col induced increased lipid peroxidase activity, which was significantly reversed by OS (as seen from the reductions in the malondialdehyde level and stabilized the rise in superoxide dismutase activity, but it had no effect on the acetylcholinesterase activity. OS might be effective in clinical AD by virtue of its cognition enhancement, antidepressant and antianxiety properties, which are the primary needs to be addressed in AD.

  9. Role of mu- and delta-opioid receptors in the nucleus accumbens in turning behaviour of rats.

    NARCIS (Netherlands)

    Matsuzaki, S.; Ikeda, H.; Akiyama, G.; Sato, M.; Moribe, S.; Suzuki, T.; Nagase, H.; Cools, A.R.; Koshikawa, N.

    2004-01-01

    The role of mu-, delta1- and delta2-opioid receptors in the nucleus accumbens in pivoting was investigated in freely moving rats. Unilateral injections of the mu-opioid receptor agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO, 1 and 2 microg) and the delta2-opioid receptor agonist, deltorphin

  10. Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats

    Science.gov (United States)

    Arnnaud, Sara B.; Harper, J. S.; Gosselink, K. L.; Navidi, M.; Fung, P.; Grindeland, R. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.

  11. Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats

    Science.gov (United States)

    Arnnaud, Sara B.; Harper, J. S.; Gosselink, K. L.; Navidi, M.; Fung, P.; Grindeland, R. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.

  12. The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model­

    Science.gov (United States)

    VandenBroeke, Marie; Youn, Jiun; Ellenbroek, Arabella K.; Karel, Peter; Shan, Ling; van Boxtel, Ruben; Ooms, Sharon; Balemans, Monique; Langedijk, Jacqueline; Muller, Mareike; Vriend, Gert; Cools, Alexander R.; Cuppen, Edwin; Ellenbroek, Bart A.

    2016-01-01

    ABSTRACT Social cognition is an endophenotype that is impaired in schizophrenia and several other (comorbid) psychiatric disorders. One of the modulators of social cognition is dopamine, but its role is not clear. The effects of dopamine are mediated through dopamine receptors, including the dopamine D1 receptor (Drd1). Because current Drd1 receptor agonists are not Drd1 selective, pharmacological tools are not sufficient to delineate the role of the Drd1. Here, we describe a novel rat model with a genetic mutation in Drd1 in which we measured basic behavioural phenotypes and social cognition. The I116S mutation was predicted to render the receptor less stable. In line with this computational prediction, this Drd1 mutation led to a decreased transmembrane insertion of Drd1, whereas Drd1 expression, as measured by Drd1 mRNA levels, remained unaffected. Owing to decreased transmembrane Drd1 insertion, the mutant rats displayed normal basic motoric and neurological parameters, as well as locomotor activity and anxiety-like behaviour. However, measures of social cognition like social interaction, scent marking, pup ultrasonic vocalizations and sociability, were strongly reduced in the mutant rats. This profile of the Drd1 mutant rat offers the field of neuroscience a novel genetic rat model to study a series of psychiatric disorders including schizophrenia, autism, depression, bipolar disorder and drug addiction. PMID:27483345

  13. Comparison of conventional and supported liquid extraction methods for the determination of sitagliptin and simvastatin in rat plasma by LC-ESI-MS/MS

    Institute of Scientific and Technical Information of China (English)

    B. Ramesha; N. Manjulaa; S.R. Bijargib; V.U.M. Sarmaa; P. Sita Devia

    2015-01-01

    Three extraction methods were compared for their efficiency to analyze sitagliptin and simvastatin in rat plasma by LC–MS/MS, including (1) liquid–liquid extraction (LLE), (2) solid phase extraction (SPE) and (3) supported liquid extraction (SLE). Comparison of recoveries of analytes with different extraction methods revealed that SLE was the best extraction method. The detection was facilitated with ion trap-mass spectrometer by multiple reactions monitoring (MRM) in a positive ion mode with ESI. The transitions monitored were m/z 441.1→325.2 for simvastatin, 408.2→235.1 for sitagliptin and 278.1→260.1 for the IS. The lower limit of quantification (LLOQ) was 0.2 ng/mL for sitagliptin and 0.1 ng/mL for simvastatin. The effective SLE offers enhanced chromatographic selectivity, thus facilitating the potential utility of the method for routine analysis of biological samples along with pharmacokinetic studies.

  14. Conventional Armaments for coming decades .

    Directory of Open Access Journals (Sweden)

    S.K. Salwan

    1997-10-01

    Full Text Available Conventional arnaments have continued to play a decisive role even in the present scenario of nuclear weapons and electronic warfare. As a war-fighting technology, they are low cost, reliable, highly effective and proven in several battlefield situations. With the application of advancements in electronics, materials and manufacturing technologies, computers and propulsion technologies to conventional weapon systems, they are capable of having greater flexibility, lethality , accuracy and effectiveness. This communication gives an overview on advancements in conventional armament systems, emerging trends in weapon technologies and modern enabling technologies for advanced weapon systems.

  15. Modulatory role of chelating agents in diet-induced hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Heba M. Mahmoud

    2014-06-01

    Conclusion: Pretreatment of hypercholesterolemic rats with simvastatin, CaNa2EDTA or DMSA attenuated most of the changes induced by feeding rats with cholesterol-rich diet owing to their observed anti-hyperlipidemic and antioxidant properties.

  16. The role of the hypothalamic nitric oxide in the pressor responses elicited by acute environmental stress in awake rats.

    Science.gov (United States)

    Kawa, T; Takeda, K; Harada, S; Hatta, T; Moriguchi, J; Miki, S; Morimoto, S; Itoh, H; Nakata, T; Sasaki, S; Nakagawa, M

    2002-08-09

    We quantitatively investigated the change in nitric oxide (NO) in the hypothalamic paraventricular nucleus (PVN) and its effect on cardiovascular regulation during shaker stress (SS) using brain microdialysis in awake rats. Male Wistar rats were fed either N(G)-nitro-L-arginine methyl ester (L-NAME, 0.7 g/L) or tap water for 2 weeks. Two days after implantation of an arterial catheter and guide shaft, a microdialysis probe was placed to perfuse the PVN with degassed Ringer solution at 2 microl/min in awake normotensive Wistar (CONTROL) and chronic L-NAME-treated hypertensive rats. After the rat was placed in a plastic cage set on a shaker, the blood pressure and heart rate was monitored and 10-min SS was loaded at a frequency of 200 cycles/min. Dialysate samples were analyzed by NO analyzer (based on the Griess reaction) every 10 min, and NOx (NO(2)(-) + NO(3)(-)) was measured. Plasma NOx was also measured before and after SS. Pressor responses elicited by SS were significantly greater in L-NAME-treated rats than in the CONTROL. Although NOx in the PVN dialysate were increased by SS in the CONTROL, these responses were attenuated in chronic L-NAME-treated rats. Resting plasma NOx were higher in the CONTROL than in L-NAME-treated rats. SS elicited no difference between two groups in plasma NOx. These results indicated that NO within the PVN, but not in systemic circulation, may play a role on the attenuation of the pressor responses elicited by SS. The dysfunction of NO release within the PVN may, in part, play a role in the exaggerated pressor responses in acute environmental stress.

  17. Propofol treatment modulates neurite extension regulated by immunologically challenged rat primary astrocytes: a possible role of PAI-1.

    Science.gov (United States)

    Ko, Hyun Myung; Joo, So Hyun; Lee, Sung Hoon; Kim, Hee Jin; Lee, Seung-Hyun; Cheong, Jae Hoon; Ryu, Jong Hoon; Kim, Jeong Min; Koo, Bon-Nyeo; Shin, Chan Young

    2015-04-01

    Propofol, a widely used anesthetic, regulates neurological processes including neurotoxicity, neuroprotection, glial activation, synaptic plasticity and neuronal maturation. Tissue plasminogen activator/tissue plasminogen activator inhibitor-1 (tPA/PAI-1) in CNS acts as a neuromodulator regulating synaptic plasticity, neurite outgrowth, seizure spreading and cell survival. Here, we investigated the effects of propofol on tPA/PAI-1 system using cultured neurons and astrocytes and their role in the regulation of neurite extension. Cultured rat primary astrocytes were treated with propofol (1-10 µM) and LPS (10 ng/ml). The expression of functional tPA/PAI-1 was examined by casein zymography, Western blot and RT-PCR. Alternatively, culture supernatants were added to cultured rat primary neuron to investigate the effects on neurite extension. Propofol alone did not affect tPA activity in rat primary cortical neuron. Similarly, propofol alone changed neither tPA nor PAI-1 activity in rat primary astrocytes. In immunologically challenged situation using LPS, propofol synergistically increased expression of PAI-1 in rat primary astrocytes without affecting tPA expression in a manner dependent on MAPKs activation. Increased expression of PAI-1 reduced tPA activity in LPS plus propofol-treated rat primary astrocytes. Consistent with the critical role of tPA activity in the regulation of neurite extension (Cho et al. 2013), the diminished tPA activity in astrocyte culture supernatants resulted in decreased neurite extension when administered to cultured rat primary cortical neuron. The results from the present study suggest that propofol, especially in immunologically-challenged situation, dysregulates tPA/PAI-1 system in brain. Whether the dysregulated tPA/PAI-1 activity adversely affects neural differentiation as well as regeneration of neuron in vivo should be empirically determined in the future.

  18. The Role of Endogenous Carbon Monoxide in the Hypoxic Vascular Remodeling of Rat Model of Hypoxic Pulmonary Hypertension

    Institute of Scientific and Technical Information of China (English)

    甄国华; 张珍祥; 徐永健

    2003-01-01

    We investigated the expression of heme oxygenase-1 (HO-l) gene and production of endogenous carbon monoxide (CO) in the rat lung tissue at different time points of chronic hypoxic pulmonary hypertension and the effect of hemin on the expression of HO-1 gene and pulmonary hypertension. A rat model of hypoxic pulmonary hypertension was recreated by exposure to intermittent normobaric hypoxic environment (10 % O2 ). Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the level of HO-1 mRNA in the rat lung tissue and double wave length spectrophotometry was used to evaluate the quantity of COHb in arterial blood. Cardiac catheterization was employed to measure the right ventricular systolic pressure (RVSP) and HE staining was performed in dissected lung tissue to observe the pathological changes of the intra-acinar pulmonary arteries (IAPA). It was found that (1) There was a low level of HO-1 mRNA in normal rat lung tissue, but the level of HO-1 mRNA increased by 2-4 times in the lung tissue of hypoxic rats (P<0.01). The quantity of COHb was 2-3 times those of control group (P<0.01or P<0. 05). These were accompanied by the increased of RVSP and the thickened IAPA; (2) Hemin could keep the HO-1 mRNA and COHb in the hypoxic rat lung tissue at a high level, and partially suppressed the increase of rat RVSP, thereby ameliorating the pathological changes of IAPA.In conclusion, the upregulation of the expression of HO-1 gene and production of CO in the rat lung of hypoxic pulmonary hypertension plays a role of inhibition in the development of hypoxic pulmonary hypertension. Hemin has a therapeutic effect on hypoxic pulmonary hypertension.

  19. Lipolytic effects of conventional β3-adrenoceptor agonists and of CGP 12,177 in rat and human fat cells : preliminary pharmacological evidence for a putative β4-adrenoceptor

    Science.gov (United States)

    Galitzky, Jean; Langin, Dominique; Verwaerde, Patrick; Montastruc, Jean-Louis; Lafontan, Max; Berlan, Michel

    1997-01-01

    The nature of rat and human fat cell β3-adrenoceptors was investigated by studying the effects of the new β3-adrenoceptor selective antagonist, SR 59,230A, on lipolysis induced by the conventional β3-adrenoceptor agonists, CL 316,243 and SR 58,611A, and by the non-conventional partial β3-adrenoceptor agonist CGP 12,177 (a potent β1- and β2-adrenoceptor antagonist with partial β3-adrenoceptor agonist property). In rat fat cells, the rank order of potency of agonists was: CL 316,243>isoprenaline>SR 58,611A>CGP 12,177. The three former agents were full agonists whereas CGP 12,177 was a partial agonist (intrinsic activity of 0.70). In human fat cells, the lipolytic effect of CGP 12,177 reached 25 % of isoprenaline effect. CL 316,243 was a poor inducer of lipolysis and SR 58,611A was ineffective. In rat fat cells, lipolysis induced by CL 316,243 and SR 58,611A was competitively antagonized by SR 59,230A. Schild plots were linear with pA2 values of 6.89 and 6.37, respectively. Conversely, 0.1, 0.5 and 1 μM SR 59,230A did not modify the concentration-response curve of CGP 12,177. A rightward shift of the curve was however observed with 10 and 100 μM of SR 59,230A. The apparent pA2 value was 5.65. The non-selective β-adrenergic antagonist, bupranolol, competitively displaced the concentration-response curve of CGP 12,177 and CL 316,243. Schild plots were linear with pA2 values of 6.70 and 7.59, respectively. CL316,243-mediated lipolytic effect was not antagonized by CGP 20,712A. In human fat cells, CGP 12,177-mediated lipolytic effect was antagonized by bupranolol and CGP 20,712A. SR 59,230A (0.1, 1 and 10 μM) did not modify the concentration-response curve of CGP 12,177. A rightward shift was however observed at 100 μM leading to an apparent pA2 value of 4.32. The results suggest that the non-conventional partial agonist CGP 12,177 can activate lipolysis in fat cells through the interaction with a β-adrenoceptor pharmacologically distinct from the β3

  20. A role for rat inositol polyphosphate kinases rIPK2 and rIPK1 in inositol pentakisphosphate and inositol hexakisphosphate production in rat-1 cells.

    Science.gov (United States)

    Fujii, Makoto; York, John D

    2005-01-14

    Over 30 inositol polyphosphates are known to exist in mammalian cells; however, the majority of them have uncharacterized functions. In this study we investigated the molecular basis of synthesis of highly phosphorylated inositol polyphosphates (such as inositol tetrakisphosphate, inositol pentakisphosphate (IP5), and inositol hexakisphosphate (IP6)) in rat cells. We report that heterologous expression of rat inositol polyphosphate kinases rIPK2, a dual specificity inositol trisphosphate/inositol tetrakisphosphate kinase, and rIPK1, an IP5 2-kinase, were sufficient to recapitulate IP6 synthesis from inositol 1,4,5-trisphosphate in mutant yeast cells. Overexpression of rIPK2 in Rat-1 cells increased inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) levels about 2-3-fold compared with control. Likewise in Rat-1 cells, overexpression of rIPK1 was capable of completely converting I(1,3,4,5,6)P5 to IP6. Simultaneous overexpression of both rIPK2 and rIPK1 in Rat-1 cells increased both IP5 and IP6 levels. To reduce IPK2 activity in Rat-1 cells, we introduced vector-based short interference RNA against rIPK2. Cells harboring the short interference RNA had a 90% reduction of mRNA levels and a 75% decrease of I(1,3,4,5,6)P5. These data confirm the involvement of IPK2 and IPK1 in the conversion of inositol 1,4,5-trisphosphate to IP6 in rat cells. Furthermore these data suggest that rIPK2 and rIPK1 act as key determining steps in production of IP5 and IP6, respectively. The ability to modulate the intracellular inositol polyphosphate levels by altering IPK2 and IPK1 expression in rat cells will provide powerful tools to study the roles of I(1,3,4,5,6)P5 and IP6 in cell signaling.

  1. Protective Roles of α-lipoic Acid in Rat Model of Mitochondrial DNA4834bp Deletion in Inner Ear

    Institute of Scientific and Technical Information of China (English)

    彭炜; 胡钰娟; 钟毅; 陈蓓; 孙宇; 杨阳; 孔维佳

    2010-01-01

    The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D-galactose group, n=10), group B (D-galactose+α-lipoic acid group, n=10), group C (α-lipoic acid group, n=10), and group D (control group, n=10). Auditory brainstem response (ABR) was used to detect the hearing threshold. Colorimetry was used to analyze activity of superoxide dismutase (SOD) and...

  2. Critical role of androgen receptor in the postnatal period in male sexual behavior in rats.

    Science.gov (United States)

    Yamada, Shunji; Ohoya, Miku; Takanami, Keiko; Matsuda, Ken Ichi; Kawata, Mitsuhiro

    2015-11-16

    Gonadal hormones have a developmental role in organization of the nervous system that regulates sexually dimorphic behavior. It is well known that androgen secreted from testes in the perinatal period is converted to estrogen by aromatase in rodent brain, and that estrogen and its receptor play a pivotal role in masculinization of brain structure and function. Treatment with flutamide, an androgen receptor (AR) antagonist, during the perinatal period inhibits development of malespecific brain structure and function, suggesting that androgen signaling via AR also influences brain masculinization. In this study, we investigated which stage during the postnatal period is critical for androgen signaling in brain masculinization. The postnatal period was designated as postnatal days (PD) 0-22, and divided into stages I (PD 0-7), II (PD 8-14), and III (PD 15-22). Newborn male rats were given flutamide subcutaneously in each stage. After adulthood, the effects of postnatal flutamide treatment on brain masculinization were evaluated byanalysis of male sexual behavior. Continuous inhibition of AR throughout stages I and II caused a robust reduction of the intromission ratio and ejaculation frequency compared with other groups. AR inhibition in stage I, II, or III did not cause any change. AR inhibition had no effect onmount behavior. These results show that stage-specific AR activation in the first two postnatal weeks may contribute to brain masculinization mediating male sexual behavior in adulthood.

  3. A role for platelet-derived growth factor-BB in rat postpneumonectomy compensatory lung growth.

    Science.gov (United States)

    Yuan, Shizeng; Hannam, Vicky; Belcastro, Rosetta; Cartel, Nicholas; Cabacungan, Judy; Wang, Jinxia; Diambomba, Yenge; Johnstone, Leslie; Post, Martin; Tanswell, A Keith

    2002-07-01

    Unilateral pneumonectomy leads to compensatory growth in the residual lung, the mediators of which are largely unknown. We hypothesized, based on its other known roles in lung cell growth, that platelet-derived growth factor (PDGF)-BB would be an essential mediator of postpneumonectomy compensatory lung growth. Left-sided pneumonectomies were performed on 21-d-old rats, for comparison with sham-operated or unoperated control animals. Body weights were not different between groups. Right lung weights and DNA content were significantly increased (p < 0.05), compared with controls, by 10 d after pneumonectomy. The rate of DNA synthesis was maximal on d 5 postpneumonectomy. Total right lung PDGF-B mRNA and PDGF-BB protein increased after pneumonectomy, but were apparently tightly regulated, relative to total right lung beta-actin mRNA and protein content, respectively. However, PDGF-BB expression after pneumonectomy was apparently not purely constitutive, in that daily i.p. injections of a truncated soluble PDGF beta-receptor both reduced activation of the native PDGF beta-receptor, and attenuated increased lung DNA synthesis on d 3 after pneumonectomy. These findings are consistent with a critical role for PDGF-BB in postpneumonectomy lung growth.

  4. Underlying Mechanism of Aconitum Lizhong Acting on Experimental Hypothermia with Indigestion in Rats: Role of Ghrelin

    Directory of Open Access Journals (Sweden)

    Xin Zhao

    2012-01-01

    Full Text Available This study is aimed to investigate the Aconitum Lizhong pill (ALZ pharmacological actions on hypothermia with indigestion, especially the ghrelin roles. The littermate-matched rats were randomly divided into four groups. Control did sham operation or standard diet, Model carried out interscapular brown adipose (IBA removal with standard diet, Fat-diet did IBA removal with fat-diet, and ALZ did IBA removal and fat-diet with 4.536 g/kg/d ALZ. The potency of adaptive thermogenesis, ghrelin levels in plasma or gastric mucosa, thyroid hormones and metabolite in sera, expression of ghrelin mRNA, and protein in gastric mucous membrane were determined. ALZ relieved the hypothermia processes with indigestion, via inhibiting ghrelin expression and increasing ghrelin secretion; the dynamics from the therapy is supported with the energy changes as less body weight loss, less plasma lipid decrease, more plasma T3 or T4 increase with TSH decrease, and more compensation of thermogenic AUC decrease. Ghrelin played key roles in the actions of ALZ on the hypothermia with indigestion. The pharmacological mechanisms of ALZ involved the homeostasis of ghrelin expression and secretion.

  5. Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage.

    Science.gov (United States)

    Park, Jonghyuck; Zheng, Lingxing; Marquis, Andrew; Walls, Michael; Duerstock, Brad; Pond, Amber; Vega-Alvarez, Sasha; Wang, He; Ouyang, Zheng; Shi, Riyi

    2014-04-01

    Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the elevation lasted at least 2 weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health.

  6. Inhibitory role of the serotonergic system on estrogen receptor α expression in the female rat hypothalamus.

    Science.gov (United States)

    Ito, Hiroyuki; Shimogawa, Yuji; Kohagura, Daisuke; Moriizumi, Tetsuji; Yamanouchi, Korehito

    2014-11-07

    The role of the serotonergic system in regulating the expression of estrogen receptor (ER) α in the hypothalamus was investigated in ovariectomized rats by injecting a serotonin synthesis inhibitor, parachlorophenylalanine (PCPA), or by destroying the dorsal raphe nucleus (DR). The number of ERα-immunoreactive (ir) cells was counted in the anteroventral periventricular nucleus in the preoptic area (AVPV), ventrolateral ventromedial hypothalamic nucleus (vlVMN), and arcuate nucleus (ARCN). Seven days after ovariectomy, 100mg/kg PCPA or saline was injected daily for 4 days. Alternatively, radiofrequency lesioning of the DR (DRL) or sham lesions were made on the same time of ovariectomy. One-day after the last injection of PCPA or 7 days after brain surgery, the brain was fixed for immunostaining of ERα and the number of ERα-ir cell were counted in the nuclei of interest. The mean number of ERα-ir cells/mm(3) (density) in the AVPV of the PCPA or DRL groups was statistically higher than that in the saline or sham group. In the vlVMN and ARCN of the PCPA or DRL groups, the mean density of ERα-ir cells was comparable to the saline or sham groups. These results suggest that the serotonergic system of the DR plays an inhibitory role on the expression of ERα in the AVPV, but not in the vlVMN and ARCN. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage

    Science.gov (United States)

    Park, Jonghyuck; Zheng, Lingxing; Marquis, Andrew; Walls, Michael; Duerstock, Brad; Pond, Amber; Alvarez, Sascha Vega; He, Wang; Ouyang, Zheng; Shi, Riyi

    2014-01-01

    Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in SCI, mainly based on in vitro and ex vivo evidence. Here we demonstrate an increase of acrolein up to 300%; the elevation lasted at least two weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health. PMID:24286176

  8. Role of neutrophilic inflammation in ozone-induced epithelial alterations in the nasal airways of rats

    Science.gov (United States)

    Cho, Hye Youn

    Ozone is a principal oxidant air pollutant in photochemical smog. Epithelial cells lining the centriacinar region of lung and the proximal aspects of nasal passage are primary target sites for ozone-induced injury in laboratory animals. Acute exposure of rats to high ambient concentrations of ozone (e.g., 0.5 ppm) results in neutrophilic inflammation, epithelial hyperplasia and mucous cell metaplasia (MCM) in the nasal transitional epithelium (NTE) lining the proximal nasal airways. The principal purpose of the present study was to investigate the role of pre-metaplastic cellular responses, especially neutrophilic inflammation, in the pathogenesis of ozone-induced MCM in rat NTE. For this purpose, three specific hypotheses-based whole-animal inhalation studies were conducted. Male F344/N rats were exposed in whole-body inhalation chambers to 0 (filtered air) or 0.5 ppm ozone for 1-3 days (8 h/day). Histochemical, immunochemical, molecular and morphometric techniques were used to investigate the ozone-induced cellular and molecular events in the NTE. Two in vitro studies were also conducted to examine the effects of ozone-inducible cytokines (i.e., tumor necrosis factor-alpha; TNF- a, and interleukin-6; IL-6) on mucin gene (rMuc-5AC) expression. Ozone induced a rapid increase of rMuc-5AC mRNA in nasal tissues within hours after the start of exposure. It preceded the appearance of MCM, and persisted with MCM. Ozone-induced neutrophilic inflammation accompanied the mucin gene upregulation, but was resolved when MCM first appeared in the NTE. Antibody-mediated depletion of circulating neutrophils attenuated ozone-induced MCM, although it did not affect the ozone-induced epithelial hyperplasia and mucin mRNA upregulation. In another study, it was found that preexisting neutrophilic rhinitis induced by endotoxin augmented the ozone-induced MCM. However, pre-existing rhinitis did not alter the severity of ozone-induced epithelial hyperplasia and mucin gene upregulation

  9. Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Jiang, Chunyang [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Department of Thoracic Surgery, Tianjin Union Medicine Centre, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin (China); Liu, Hongliang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Guan, Zhizhong [Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou (China); Zeng, Qiang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Cui, Yushan; Yu, Linyu [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Wang, Zhenglun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Wang, Aiguo, E-mail: wangaiguo@mails.tjmu.edu.cn [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China)

    2013-09-01

    Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: • We used a rat model to simulate the situations of human fluoride (F) exposure. • Developmental F exposure induces testicular damage related with oxidative stress.

  10. The role of cyclooxygenase-2/prostanoid pathway in visceral pain induced liver stress response in rats

    Institute of Scientific and Technical Information of China (English)

    PISTON Donald; WANG Shan; FENG Yi; YE Ying-jiang; ZHOU Jing; JIANG Ke-wei; XU Feng; ZHAO Yong; CUI Zhi-rong

    2007-01-01

    Background Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostanoids from arachidonic acid.COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway.Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/reperfusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.Methods Fifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase (GST) activity, COX-2 mRNA, prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-Ketone-prostaglandin F1α (6-K-PGF1α) contents were assessed.Results Thirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group (P<0.01 and P<0.05 respectively), accompanied by colonic inflammation. Liver GST activity levels significantly dropped (P<0.05). Liver COX-2 mRNA expression significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1α concentrations. NS398 and morphine both ameliorated post-stress liver GST activity (P<0.05 and P<0.01respectively), decreased stress

  11. Hyposensitivity to nerve stimulation in portal hypertensive rats: role of nitric oxide.

    Science.gov (United States)

    Sieber, C C; Sumanovski, L T; Moll-Kaufmann, C; Stalder, G A

    1997-11-01

    Portal hypertension goes along with vascular hyporeactivity, partly mediated by nitric oxide (NO). Interactions between the adrenergic nervous system and NO in portal hypertension are undetermined. We tested (1) whether superior mesenteric arterial beds of portal hypertensive rats have an altered sensitivity to periarterial nerve stimulation (PNS) and (2) the role of NO in modulating nerve-stimulated responses. Vasopressor responses to PNS (Hz, 2-32) were similar in preparations of partial portal vein-ligated (PVL, n = 12) and control (CON, n = 12) rats (60.0 +/- 6.7 and 47.8 +/- 6.1 CmH2O respectively) for 24 Hz (NS), but sensitivity of vessels of portal hypertensive animals displayed a significant rightward shift [Hz needed for 50% of maximal response (HZ50) being 15.5 +/- 0.4 and 12.9 +/- 0.6 for PVL and CON respectively, P < 0.001]. NO formation inhibition by N omega-nitro-L-arginine (10(-4) mol L-1) significantly increased responses to PNS (P < 0.05), the absolute values for 24 Hz being 101.4 +/- 11.7 cmH2O for PVL (n = 8) and 86.4 +/- 11.4 cmH2O for CON (n = 7) (NS). NO formation inhibition reversed the hyposensitivity in preparations of PVL, Hz50 being 13.9 +/- 0.5 and 13.2 +/- 0.2 for PVL and CON respectively (NS). Adrenergic receptor antagonism with prazosin (10(-7) mol L-1) and yohimbine (10(-6) mol L-1) inhibited PNS-mediated vasopressor reactivity (n = 6 per group, P < 0.001), confirming the nervous origin of vasoconstrictor responses. It is concluded that (1) portal hypertension goes along with a significant hyposensitivity to PNS and (2) this hyposensitivity is reversed by NO-formation inhibition

  12. The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain

    Science.gov (United States)

    Kim, Do Yun; Chae, Joo Wung; Lim, Chang Hun; Heo, Bong Ha; Park, Keun Suk; Lee, Hyung Gon; Choi, Jeong Il; Yoon, Myung Ha

    2016-01-01

    Background Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level. PMID:27413481

  13. Role of Y(2) receptors in the regulation of gastric tone in rats.

    Science.gov (United States)

    Janssen, P; Verschueren, S; Rotondo, A; Tack, J

    2012-04-01

    We set out to determine the effect of peptide YY(3-36) (PYY(3-36)) on the gastric muscle tone in conscious rats by measuring intragastric pressure (IGP) during intragastric nutrient drink infusion. After an overnight fast, a chronically implanted gastric fistula was connected to a custom-made nutrient drink infusion system and a catheter to measure IGP. IGP was measured before and during the infusion of a nutrient drink (Nutridrink; 0.5 ml/min) until 10 ml was infused. Rats were treated with PYY(3-36) (0, 33, and 100 pmol·kg(-1)·min(-1)) in combination with a subcutaneous injection of the Y(2) receptor antagonists JNJ31020028 (10 mg/kg) or BIIE0246 (2 mg/kg). Experiments were also performed after subdiaphragmatic vagotomy and after pretreatment with 3 ml of nutrient drink (to mimic a fed state). IGP was compared as the average IGP during nutrient infusion, represented as means ± SE and compared using ANOVA. PYY(3-36) dose dependently increased the IGP during nutrient infusion (4.7 ± 0.3, 5.7 ± 0.5 and 7.3 ± 0.7 mmHg; P IGP during, an effect attenuated by JNJ31020028. BIIE0246 and JNJ31020028 were not able to decrease the IGP when no PYY(3-36) was administered. PYY(3-36) increased gastric tone through an Y(2) receptor-mediated mechanism that does not involve the vagus nerve. Y(2) receptor antagonists were not able to decrease gastric tone without exogenous administration of PYY(3-36), indicating that Y(2) receptors do not play a crucial role in the determination of gastric tone in physiological conditions.

  14. Role of endothelium in angiotensin II formation by the rat aorta and mesenteric arterial bed

    Directory of Open Access Journals (Sweden)

    R. Leite

    1997-05-01

    Full Text Available We investigated the angiotensin II (Ang II-generating system by analyzing the vasoconstrictor effect of Ang II, angiotensin I (Ang I, and tetradecapeptide (TDP renin substrate in the absence and presence of inhibitors of the renin-angiotensin system in isolated rat aortic rings and mesenteric arterial beds with and without functional endothelium. Ang II, Ang I, and TDP elicited a dose-dependent vasoconstrictor effect in both vascular preparations that was completely blocked by the Ang II receptor antagonist saralasin (50 nM. The angiotensin converting enzyme (ACE inhibitor captopril (36 µM completely inhibited the vasoconstrictor effect elicited by Ang I and TDP in aortic rings without affecting that of Ang II. In contrast, captopril (36 µM significantly reduced (80-90% the response to bolus injection of Ang I, without affecting those to Ang II and TDP in mesenteric arteries. Mechanical removal of the endothelium greatly potentiated (70-95% the vasoconstrictor response to Ang II, Ang I, and TDP in aortic rings while these responses were unaffected by the removal of the endothelium of mesenteric arteries with sodium deoxycholate infusion. In addition, endothelium disruption did not change the pattern of response elicited by these peptides in the presence of captopril. These findings indicate that the endothelium may not be essential for Ang II formation in rat mesenteric arteries and aorta, but it may modulate the response to Ang II. Although Ang II formation from Ang I is essentially dependent on ACE in both vessels, our results suggest the existence of an alternative pathway in the mesenteric arterial bed that may play an important role in Ang II generation from TDP in resistance but not in large vessels during ACE inhibition

  15. Role of Calcium Channels in the Protective Effect of Hydrogen Sulfide in Rat Cardiomyoblasts

    Directory of Open Access Journals (Sweden)

    Daniele Avanzato

    2014-04-01

    Full Text Available Background: Hydrogen sulfide contributes to the reduction of oxidative stress-related injury in cardiomyocytes but the underlying mechanism is still unclear. Aims: Here we investigated the role of voltage-operated calcium channels (VOCCs as mediators of the beneficial effect of H2S against oxidative stress in cultured rat cardiomyoblasts (H9c2. Methods: Intracellular calcium signals were measured by fluorimetric live cell imaging and cell viability by colorimetric assay. Results: Treatment with H2S donor (NaHS 10 µM or Nifedipine (10 µM decreased resting intracellular calcium concentration [Ca]i, suggesting that L-type VOCCs are negatively modulated by H2S. In the presence of Nifedipine H2S was still able to lower [Ca]i, while co-incubation with Nifedipine and Ni2+ 100 µM completely prevented H2S-dependent [Ca]i decrease, suggesting that both L-type and T-type VOCCs are inhibited by H2S. In addition, in the same experimental conditions, H2S triggered a slow increase of [Ca]i whose molecular nature remains to be clarified. Pretreatment of H9c2 with NaHS (10 µM significantly prevented cell death induced by H2O2. This effect was mimicked by pretreatment with L-Type calcium channel inhibitor Nifedipine (10 µM. Conclusions: The data provide the first evidence that H2S protects rat cardiomyoblasts against oxidative challenge through the inhibition of L-type calcium channels.

  16. Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.

    Science.gov (United States)

    Konturek, S J; Dembinski, A; Konturek, P J; Warzecha, Z; Jaworek, J; Gustaw, P; Tomaszewska, R; Stachura, J

    1992-01-01

    The importance of platelet activating factor in acute pancreatitis was examined by determining the tissue content of endogenous platelet activating factor and the protective effects of TCV-309, a highly selective platelet activating factor blocker, against caerulein induced pancreatitis in rats. Infusion of caerulein (10 micrograms/kg/h) for five hours resulted in about 70% increase in pancreatic weight, 22% rise in protein content, 50% reduction in tissue blood flow, nine fold increase in tissue level of platelet activating factor and 165% rise in plasma amylase as well as histological evidence of acute pancreatitis. Such infusion of caerulein in chronic pancreatic fistula rats caused a marked increase in protein output from basal secretion of 10 mg/30 minutes to 40 mg/30 minutes in the first hour of infusion followed by a decline in protein output to 15-20 mg/30 minutes in the following hours of the experiment. Exogenous platelet activating factor (50 micrograms/kg) injected ip produced similar alterations in weight, protein content, blood flow, and histology of the pancreas but the increment in serum amylase was significantly smaller and pancreatic secretion was reduced below the basal level. TCV-309 (50 micrograms/kg) given ip before caerulein or platelet activating factor administration significantly reduced the biochemical and morphological alterations caused by caerulein and abolished those induced by exogenous platelet activating factor. These results indicate that platelet activating factor plays an important role in the pathogenesis of acute pancreatitis probably by reducing the blood flow and increasing vascular permeability in the pancreas. PMID:1385272

  17. Role of PGI2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Zhi-Yong Wu; Xue-Song Chen; Jiang-Feng Qiu; Hui Cao

    2005-01-01

    AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH)group by injection of CCl4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitroL-arginine (L-NNA)group (n = 21) group, indomethacin (INDO)group (n = 22) and high-dose heparin group (n = 24). The for one week, then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-)levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α,a stable hydrolytic product of PGI2, was determined by radioimmunoassay.RESULTS: The concentrations of plasma 6-keto-PGF1α(pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats(1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11,75.21±6.89) were significantly higher than those in SO rats(725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF1α and serum NO2-/NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP,TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of

  18. Role of lipooligosaccharide in virulence of the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius for infant rats.

    Science.gov (United States)

    Rubin, L G; St Geme, J W

    1993-02-01

    Clonally related strains of Haemophilus influenzae biogroup aegyptius have recently been associated with Brazilian purpuric fever (BPF), a fulminant, systemic disease in children. Using an infant rat bacteremia model for BPF, we found that a rat blood-passaged BPF isolate of H. influenzae biogroup aegyptius was more virulent than the original strain was. When compared with the original strain, the animal-passaged variant was found to display an altered lipooligosaccharide (LOS) phenotype and to lack pili. To examine the role of LOS phenotype and pili in virulence, we isolated isogenic variants differing in LOS phenotype or expression of pili. The virulence of variants was compared by examining the results of blood cultures obtained 24 h after intraperitoneal inoculation with 10(5) CFU. Our results indicate that the LOS phenotype is a critical determinant of BPF clone virulence for infant rats. To a lesser extent, the absence of piliation and an undefined additional factor(s) contribute to virulence.

  19. Role of delayed gastric emptying in the pathogenesis of cysteamine-induced duodenal ulcer in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1982-01-01

    Cysteamine is a potent duodenal ulcerogen in rats. It has been demonstrated to inhibit gastric empyting, whose role in ulcer formation is unknown. In the present study the effect of cysteamine on gastric motility and emptying rate in rats was studied by direct fluoroscopic observation. The delayed....... After 4 h this pool of undiluted gastric secretions gradually is emptied into the duodenum, where the mucosal resistance is reduced by inhibition of the secretory activity of Brunner's glands, and ulceration rapidly develops. The time relationship is supported by histopathologic findings...... and measurements of gastric acid secretions after cysteamine. Vagotomy augmented the inhibitory effect of cysteamine on gastric motility. The relaxation was even more pronounced, and contrast medium was not discharged from the stomach within 24 h. In these rats cysteamine induced ulcerations in the stomach....

  20. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

    Science.gov (United States)

    Kushwah, Neetu; Jain, Vishal; 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.

  1. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

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    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 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.

  2. The role of α7 nicotinic acetylcholine receptor in modulation of heart rate dynamics in endotoxemic rats.

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    Roham Mazloom

    Full Text Available Previous reports have indicated that artificial stimulation of the vagus nerve reduces systemic inflammation in experimental models of sepsis. This phenomenon is a part of a broader cholinergic anti-inflammatory pathway which activates the vagus nerve to modulate inflammation through activation of alpha7 nicotinic acetylcholine receptors (α7nACHR. Heart rate variability represents the complex interplay between autonomic nervous system and cardiac pacemaker cells. Reduced heart rate variability and increased cardiac cycle regularity is a hallmark of clinical conditions that are associated with systemic inflammation (e.g. endotoxemia and sepsis. The present study was aimed to assess the role of α7nACHR in modulation of heart rate dynamics during systemic inflammation. Systemic inflammation was induced by injection of endotoxin (lipopolysaccharide in rats. Electrocardiogram and body temperature were recorded in conscious animals using a telemetric system. Linear and non-linear indices of heart rate variability (e.g. sample entropy and fractal-like temporal structure were assessed. RT-PCR and immunohistochemistry studies showed that α7nACHR is expressed in rat atrium and is mainly localized at the endothelial layer. Systemic administration of an α7nACHR antagonist (methyllycaconitine did not show a significant effect on body temperature or heart rate dynamics in naïve rats. However, α7nACHR blockade could further reduce heart rate variability and elicit a febrile response in endotoxemic rats. Pre-treatment of endotoxemic animals with an α7nACHR agonist (PHA-543613 was unable to modulate heart rate dynamics in endotoxemic rats but could prevent the effect of endotoxin on body temperature within 24 h experiment. Neither methyllycaconitine nor PHA-543613 could affect cardiac beating variability of isolated perfused hearts taken from control or endotoxemic rats. Based on our observations we suggest a tonic role for nicotinic acetylcholine

  3. The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

    Science.gov (United States)

    Asgar, J; Zhang, Y; Saloman, J L; Wang, S; Chung, M-K; Ro, J Y

    2015-12-03

    Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,β-methylene adenosine triphosphate (αβmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain

  4. Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress

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    Didem Onk

    2016-01-01

    Full Text Available Background. Inflammation and oxidative stress (OxS contribute to the pathogenesis of diabetic kidney disease (DKD and contrast-induced nephropathy (CIN. Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33 is a proinflammatory cytokine, but its role in DKD and CIN is unknown. Methods. Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs, whereas the other four groups were made up of diabetic rats (DRs, diabetic rats with contrast-induced nephropathy (CIN + DRs, melatonin-treated diabetic rats (MTDRs, and melatonin-treated CIN + DRs (MTCIN + DRs. All groups except the HRs received 50 mg/kg/day streptozotocin (STZ. CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT from the 28th day for the constitutive seven days. Results. We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p<0.05. Conclusion. Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.

  5. Role of N-Nitro-L-Arginine-Methylester as anti-oxidant in transient cerebral ischemia and reperfusion in rats

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    Awooda Hiba A

    2013-01-01

    Full Text Available Abstract Background Previous reports assessing the neuroprotective role of nonselective Nitric Oxide synthase (NOS inhibitor N-nitro-L-arginine-methylester (L-NAME following cerebral ischemia/reperfusion are contradictory. The aim of this work was to examine the potential benefits of L-NAME on rats subjected to transient focal cerebral ischemia/reperfusion. Methods The study involved 30 adult male Wistar rats divided into three groups 10 rats in each: First group was sham-operated and served as a control, a ischemia/reperfusion (I/R group of rats infused with 0.9% normal saline intraperitoneally 15 minutes prior to 30 minutes of left common carotid artery (CCA occlusion and a test group infused with L-NAME intraperitoneally 15 minutes prior to ischemia. Neurobehavioral assessments were evaluated and quantitative assessment of malondialdehyde (MDA, Nitric oxide (NO metabolites and total antioxidant capacity (TAC in both serum and the affected cerebral hemisphere were achieved. Results Rats’ neurological deficit and TAC were significantly decreased while NO and MDA were significantly increased in the I/R compared with the control group (P Conclusions L-NAME pretreatment for rats undergoing cerebral ischemia/reperfusion significantly improves neurological deficit while reducing oxidative stress biomarkers in the affected cerebral hemisphere.

  6. Potential role of Saudi red propolis in alleviating lung damage induced by methicillin resistant Staphylococcus aureus virulence in rats.

    Science.gov (United States)

    Saddiq, Amna Ali; Mohamed, Azza Mostafa

    2016-07-01

    The aim of this study was to explore the protective impact of aqueous extract of Saudi red propolis against rat lung damage induced by the pathogenic bacteria namely methicillin resistant Staphylococcus aureus (MRSA) ATCC 6538 strain. Infected rats were received a single intraperitoneal (i.p.) injection of bacterial suspension at a dose of 1 X 10(6) CFU / 100g body weight. Results showed that oral administration of an aqueous extract of propolis (50mg/100g body weight) daily for two weeks to infected rats simultaneously with bacterial infection, effectively ameliorated the alteration of oxidative stress biomarker, malondialdehyde (MDA), as well as the antioxidant markers, glutathione peroxidase (GPx) and superoxide dismutase (SOD), in lungs of infected rats compared with infected untreated ones. Also, the used propolis extract successfully modulated the alterations in proinflammatory mediators, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in serum. In addition, the propolis extract successfully modulated the oxidative DNA damage and the apoptosis biomarker, caspase 3, in lungs of S aureus infected rats compared with infected untreated animals. The biochemical results were supported by histo-pathological observation of lung tissues. In conclusion, the beneficial prophylactic role of the aqueous extract of Saudi red propolis against lung damage induced by methicillin resistant S aureus may be related to the antioxidant, anti-inflammatory, immunomodulatory and antiapoptosis of its active constituents.

  7. Role of 5-HT7 receptors in the inhibition of the vasodepressor sensory CGRPergic outflow in pithed rats.

    Science.gov (United States)

    Cuesta, Cristina; García-Pedraza, José Ángel; García, Mónica; Villalón, Carlos M; Morán, Asunción

    2014-10-01

    The role of calcitonin gene-related peptide (CGRP) in the modulation of vascular tone has been widely documented. Indeed, electrical stimulation of the perivascular sensory outflow in pithed rats induces vasodepressor responses by activation of CGRP receptors. This study investigated the role of 5-HT7 receptors in the inhibition of the rat vasodepressor sensory outflow. Male Wistar pithed rats were pretreated with i.v. continuous infusions of hexamethonium and methoxamine, followed by physiological saline or AS-19 (a 5-HT7 receptor agonist). Then, electrical stimulation of the spinal cord resulted in frequency-dependent decreases in DBP. The infusions of AS-19, as compared to those of saline, inhibited the vasodepressor responses induced by electrical stimulation without affecting those to i.v. bolus injections of exogenous α-CGRP. This inhibition by AS-19 was abolished by the antagonists pimozide (5-HT7) or sulfisoxazole (ETA), but not by indomethacin (COX1/2) or losartan (AT1), at doses that did not affect per se the electrically-induced vasodepressor responses. Interestingly, glibenclamide (an ATP-dependent K(+) channel blocker) attenuated these vasodepressor responses. The present results suggest that AS-19-induced inhibition of the rat vasodepressor sensory CGRPergic outflow is mainly mediated by 5-HT7 receptors via endothelin release, with the possible involvement of ATP-dependent K(+) channels.

  8. Role of Endothelial Differentiated Adipose-derived Stem Cells in Repairing Calvarial Critical Size Defects in the Laboratory Rat (Rattus norvegicus)

    Science.gov (United States)

    2014-07-16

    Differentiated Adipose-derived Stem Cells in Repairing Calvarial Critical Size Defects in the Laboratory Rat (Rattus norvegicus) PRINCIPAL INVESTIGATOR...SUBTITLE FDG20110033A "Role of Endothelial Differentiated Adipose-derived Stem Cells in Repairing Calvarial Critical Size Defects in the Laboratory Rat (Rattus

  9. Novel role for gabapentin in neuroprotection of central nervous system in streptozotocine-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Giyasettin BAYDAS; Ertugrul SONKAYA; Mehmet TUZCU; Abdullah YASAR; Emir DONDER

    2005-01-01

    Aim: To investigate the effect of gabapentin on neural [neuron-specific enolase (NSE)] and glial markers [glial fibrillary acidic protein (GFAP) and S100B] in different brain regions of diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocine (50 mg/kg body weight). Rats in one group received vehicle only for 6 weeks. The levels of GFAP, S 100B, and NSE were determined by immunoblotting in the hippocampus, cortex, and cerebellum. Lipid peroxidation (LPO as malondialdehyde+ 4-hydroxyalkenals) and glutathione (GSH) levels were also determined in the same brain parts. Results: Total and degraded GFAP content and S100B protein expression in different areas of brain tissues significantly increased in diabetic rats compared to control rats. Similarly, NSE levels were also significantly elevated in hyperglycemic rats. In addition, there was a significant increase in LPO levels in the diabetic rat brain compared to control rat brains. Pretreatment with gabapentin prevented the upregulation of GFAP, S 100B, and NSE in all brain regions of diabetic rats. The level of LPO was reduced, but not completely halted, by treatment with gabapentin. Conclusion: These results suggest that diabetes causes glial and neuronal injury, possibly as a result of elevated oxidative stress, and that gabapentin protects neurons and glial cells. Thus, we predict that gabapentin treatment will attenuate the hippocampal and cortical neurodegeneration observed during diabetes mellitus in rats.

  10. Role of spinal GABAA receptor reduction induced by stress in rat thermal hyperalgesia.

    Science.gov (United States)

    Ma, Xuelian; Bao, Weiying; Wang, Xiujun; Wang, Zhilong; Liu, Qiaoran; Yao, Zhenyu; Zhang, Di; Jiang, Hong; Cui, Shuang

    2014-11-01

    The mechanisms underlying stress-induced hyperalgesia (SIH) remain poorly understood. Recent findings have provided strong evidence indicating that SIH could be related, at least in part, to alterations in spinal cord GABA activity. In the present study, we first investigated how acute restraint stress impacted pain responses as assessed using the tail flick immersion test. These results showed that rats developed hyperalgesia at 6 h after being subjected to 1-h acute restraint stress. Second, we measured the activation of spinal neurons and alterations in expression of GABAA receptor β2 and β3 subunits as related to stress-induced hyperalgesia. Results from Western blot and immunofluorescence assays showed that c-fos protein increased in the dorsal horn of the lumbar spinal cord and GABAA receptor β2 and β3 subunit proteins decreased significantly at 6 h after exposure to 1 h of acute restraint stress. Finally, the effects of spinal GABAA receptor alteration on SIH were evaluated. These results showed that intrathecal administration of muscimol inhibited hyperalgesia induced by stress while bicuculline enhanced hyperalgesia in the control groups. Taken together, the present data reveal that GABAA receptor β2 and β3 decrease following 1 h of acute restraint stress and may play a critical role in SIH.

  11. The role of secretory granules in radiation-induced dysfunction of rat salivary glands

    Energy Technology Data Exchange (ETDEWEB)

    Peter, B.; Van Waarde, M.A.W.H.; Konings, A.W.T. [Univ. of Groningen (Netherlands); Vissink, A. [Univ. of Groningen (Netherlands)]|[Univ. Hospital, Groningen (Netherlands); `s-Gravenmade, E.J. [Univ. Hospital, Groningen (Netherlands)

    1995-02-01

    To investigate the possible role of secretory granules in radiation-induced salivary gland dysfunction, rats were pretreated with isoproterenol (5 mg/kg intraperitoneally) to degranulate salivary gland acini. At maximal depletion, salivary glands were locally irradiated with a single dose of 15 Gy of X rays. Parotid and submandibular/sublingual saliva samples were collected before and 1-10 days after irradiation. The lag phase, flow rate, concentrations of potassium and sodium, and amylase secretion were determined. Sham-treated, isoproterenol-treated and irradiated animals provided reference data. In the parotid gland, but not in the submandibular gland, protection against radiation-induced changes in flow rate and composition of saliva occurred after pretreatment with isoproterenol. Combining morphological data from a previous study with data from the current study, it is suggested that improvement of parotid gland function is attributed predominantly to a proliferative stimulus on acinar cells by isoproterenol and not to its degranulation effect. After pretreatment with isoproterenol, an earlier expression of radiation-induced acinar cell damage leading to death was observed, followed by a faster tissue recovery. Thus the proliferative stimulus on acinar cells may accelerate the unmasking of latent lethal damage, resulting in the earlier replacement of dead cells by new, functionally intact cells. 33 refs., 2 figs.

  12. Teratogenic effect of cisplatin in rats and the protective role of sodium selenate.

    Science.gov (United States)

    Hassan, Mohammed S; Morgan, Ashraf M; Mekawy, Mohey M; Zaki, Amr R; Ghazi, Zeinab M

    2016-05-01

    Eighty pregnant Sprague-Dawley rats were used in this study. They were allotted to four equal groups. The first group served as a control without any treatment while the other groups were given cisplatin, sodium selenate, and cisplatin+sodium selenate, respectively. Cisplatin was injected intraperitoneally in a dose of 5mg/kgb wt. on the 12th day of gestation while sodium selenate was administered orally in a dose of 0.5mg/kgb wt throughout gestation. Animals were sacrificed on the 20th day of gestation for fetal examination. Cisplatin produced significant elevation in the percentages of late resorption sites and dead foetuses compared with the control group. The mean foetal and placental weights were significantly reduced. Dwarf foetuses and subcutaneous (s/c) haemorrhage were also recorded in cisplatin-treated group. Visceral abnormalities were revealed in the form of dilated nares, anophthalmia and/or microphthalmia, dilated brain ventricles, hypertrophy of the heart, hypoplasia of the lung, hepatomegaly and dilated renal pelvis. Skeletal examination showed wide open fontanel, incomplete ossification of parietal and interparietal bones, incomplete ossification of sternum, reduction in the number or even complete absence of phalanges, sacral and/or caudal vertebrae. Histopathological examination of placentas in cisplatin-treated group revealed severe pathological alterations. Administration of sodium selenate significantly alleviated the afore-mentioned adverse effects of cisplatin on the fetuses and their placentas so we conclude that sodium selenate as an antioxidant has an effective protective role in cisplatin teratogenic effects.

  13. Role of cuneiform nucleus in regulation of sympathetic vasomotor tone in rats.

    Science.gov (United States)

    Shafei, Mohammad Naser; Nasimi, Ali; Alaei, Hojatallah; Pourshanazari, Ali Asghar; Hosseini, Mahmoud

    2012-06-01

    The cuneiform nucleus (CnF) is a sympathoexcitatory area involved in the central cardiovascular regulation. Its role in the maintaining vasomotor tone has, however, not yet been clarified. In the present study the effects of cobalt chloride (CoCl(2)) a nonselective synapse blocker and NMDA and non-NMDA glutamate receptors on resting mean arterial blood pressure and heart rate of CnF have been evaluated. CoCl(2), AP5 (an NMDA receptor antagonist) and CNQX (an AMPA/kinase receptor antagonist) (100nl) were microinjected into the CnF of anesthetized rats. The blood pressure and heart rate were recorded throughout the experiment. The responses of blood pressure and heart rate were compared with the pre-injection (paired t-test) and control (independent t-test) values. Microinjection of CoCl(2), AP5 and CNQX did not change the basal blood pressure and heart rate. In conclusion, our present study indicates that the CnF is not important in the regulation of cardiovascular tone. Copyright © 2011. Published by Elsevier Ireland Ltd.

  14. The Role of Monosialoganglioside GM1 in LTP-Induction in Rat Hippocampal Slices

    Institute of Scientific and Technical Information of China (English)

    李永新; 梅镇彤

    1994-01-01

    The effect of monosialoganglioside GM1 of different doses on the long-term potentiation (LTP) of synaptic transmission has been studied in the CA1 region of rat hippocampal slices, and the possible role that calcium ion and NMDA receptor play has also been investigated. The results reveal that larger magnitude of LTP is induced in hippocampal slices pre-incubated with GM1. The dose-response curve appears in diphase, and the largest magnitude of LTP has been obtained at the GM1 concentration of 50 mg/L in incubation ACSF. Moreover, the magnitude of LTP induced from the slices pre-incubated with GM1 at lower calcium ion concentration is similar to that obtained from the control slices at normal calcium ion concentration. Under higher calcium ion concentration, the enhancing effect of GM1 on LTP seems relatively feeble. After NMDA receptors were blocked, no enhancing effect of GM1 was observed. The mechanism of GM1 action on LTP is discussed.

  15. PRDM5 Expression and Essential Role After Acute Spinal Cord Injury in Adult Rat.

    Science.gov (United States)

    Liu, Jie; Wu, Weijie; Hao, Jie; Yu, Mingchen; Liu, Jin; Chen, Xinlei; Qian, Rong; Zhang, Feng

    2016-12-01

    PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products that modulate cellular processes such as differentiation, cell growth and apoptosis. PRDM5 is a recently identified family member that functions as a transcriptional repressor and behaves as a putative tumor suppressor in different types of cancer. However, the expression and function of PRDM5 in spinal cord injury (SCI) are still unknown. In the present study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of PRDM5 expression in the spinal cord. We found that PRDM5 protein levels gradually increased, reaching a peak at day 5 and then gradually declined to a normal level at day 14 after SCI with Western blot analysis. Double immunofluorescence staining showed that PRDM5 immunoreactivity was found in neurons, astrocytes and microglia. However, the expression of PRDM5 was increased predominantly in neurons. Additionally, colocalization of PRDM5/active caspase-3 was been respectively detected in neurons. In vitro, we found that depletion of PRDM5 by short interfering RNA, obviously decreases neuronal apoptosis. In summary, this is the first description of PRDM5 expression in SCI. Our results suggested that PRDM5 might play crucial roles in CNS pathophysiology after SCI and this research will provide new drug targets for clinical treatment of SCI.

  16. Metallothionein response to stress in rats: role in free radical scavenging.

    Science.gov (United States)

    Hidalgo, J; Campmany, L; Borras, M; Garvey, J S; Armario, A

    1988-10-01

    The possibility that liver metallothionein (MT) can function as an antioxidant in vivo has been studied in the rat. It was found that the stress of food and water deprivation with or without physical immobilization consistently increased liver lipid peroxidation (LLP), suggesting that liver MT induction by stress might be related to the stress-induced LLP. This was supported by results with the lipid peroxidation promoter dimethyl sulfoxide (DMSO) and the natural antioxidant vitamin E. Whereas DMSO administration increased LLP levels in basal and stress situations, vitamin E decreased them. Liver MT levels were increased by DMSO in basal and stress situations, whereas they were decreased by vitamin E during stress. These in vivo results are consistent with an antioxidant role of liver MT suggested by previous in vitro results. However, liver MT preinduction by Zn treatment did not result in a lower MT response to stress. Instead a positive synergistic effect between Zn and stress appeared to be present. This result indicates that the mechanism of action of MT as antioxidant remains unclear.

  17. The role of mitochondrial DNA large deletion for the development of presbycusis in Fischer 344 rats.

    Science.gov (United States)

    Yin, Shankai; Yu, Zhiping; Sockalingam, Ravi; Bance, Manohar; Sun, Genlou; Wang, Jian

    2007-09-01

    Age-related hearing loss, or presbycusis, has been associated with large-scale mitochondrial DNA (mtDNA) deletion in previous studies. However, the role of this mtDNA damage in presbycusis is still not clear because the deletion in inner ears has not been measured quantitatively and analyzed in parallel with the time course of presbycusis. In the present study, the deletion was quantified using quantitative real-time PCR (qRT-PCR) in male Fischer 344 rats of different ages. It was found that the deletion increased quickly during young adulthood and reached over 60% at 6 months of age. However, a significant hearing loss was not seen until after 12 months of age. The results suggest that the existence of the deletion per se does not necessarily imply cochlear damage, but rather a critical level of the accumulated deletion seems to precede the hearing loss. The long delay may indicate the involvement of mechanisms other than mtDNA deletion in the development of presbycusis.

  18. Protective Role of Aerobic Exercise Against Cisplatin-Induced Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Zeynali

    2015-09-01

    Full Text Available Background Cisplatin (CP is a chemotherapy drug and nephrotoxicity is considered as its major side effect. Aerobic exercise is well known as an approach to reduce the side effects of many drugs. Objectives This study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity. Materials and Methods Thirty male Wistar rats were randomly divided into four groups. Group I had aerobic exercise on a treadmill one hour per day and five days per week for eight weeks. Then, the exercise protocol was continued for another week, but during this week, the animals also received CP (2.5 mg/kg/day; ip. Group II underwent the same protocol as group I without exercise in the last week during the CP therapy. Groups III and IV were assigned as positive and negative control groups, and were treated with CP and saline without exercise, respectively. Finally, the animals were sacrificed for the biochemical measurement and tissue histopathology investigation. Results CP alone without exercise increased serum levels of blood urea nitrogen (BUN, creatinine (Cr, and malondialdehyde (MDA; and kidney nitrite level, while treadmill exercise in group I significantly ameliorated these parameters (P < 0.05. Kidney and serum levels of MDA and nitrite did not alter significantly. Also, the severity of kidney tissue damage decreased significantly in groups I and II (P < 0.05. Conclusions Aerobic exercise may reduce CP-induced nephrotoxicity with a favorable effect on renal function by increasing activation of antioxidant system.

  19. Cardioprotective Effects of Voluntary Exercise in a Rat Model: Role of Matrix Metalloproteinase-2

    Directory of Open Access Journals (Sweden)

    Anikó Pósa

    2015-01-01

    Full Text Available Background. Regular exercise at moderate intensity reduces cardiovascular risks. Matrix metalloproteinases (MMPs play a major role in cardiac remodeling, facilitating physiological adaptation to exercise. The aim of this study was to examine the influence of voluntary physical exercise on the MMP-2 enzyme activity and to investigate the cardiac performance by measurement of angina susceptibility of the heart, the basal blood pressure, the surviving aorta ring contraction, and the cardiac infarct size after I/R-induced injury. Methods. Male Wistar rats were divided into control and exercising groups. After a 6-week period, the serum level of MMP-2, basal blood pressure, cardiac angina susceptibility (the ST segment depression provoked by epinephrine and 30 s later phentolamine, AVP-induced heart perfusion and aorta ring contraction, infarct size following 30 min ischemia and 120 min reperfusion, and coronary effluent MMP-2 activity were measured. Results. Voluntary wheel-running exercise decreased both the sera (64 kDa and 72 kDa and the coronary effluent (64 kDa MMP-2 level, reduced the development of ST depression, improved the isolated heart perfusion, and decreased the ratio of infarct size. Conclusion. 6 weeks of voluntary exercise training preserved the heart against cardiac injury. This protective mechanism might be associated with the decreased activity of MMP-2.

  20. Role of elevated S-adenosylhomocysteine in rat hepatocyte apoptosis: protection by betaine.

    Science.gov (United States)

    Kharbanda, Kusum K; Rogers, David D; Mailliard, Mark E; Siford, Gerri L; Barak, Anthony J; Beckenhauer, Harriet C; Sorrell, Michael F; Tuma, Dean J

    2005-12-05

    Previous studies from our laboratory have shown that ethanol consumption results in an increase in hepatocellular S-adenosylhomocysteine levels. Because S-adenosylhomocysteine is a potent inhibitor of methylation reactions, we propose that increased intracellular S-adenosylhomocysteine levels could be a major contributor to ethanol-induced pathologies. To test this hypothesis, hepatocytes isolated from rat livers were grown on collagen-coated plates in Williams' medium E containing 5% FCS and exposed to varying concentrations of adenosine in order to increase intracellular S-adenosylhomocysteine levels. We observed increases in caspase-3 activity following exposure to adenosine. This increase in caspase activity correlated with increases in intracellular S-adenosylhomocysteine levels and DNA hypoploidy. The adenosine-induced changes could be significantly attenuated by betaine administration. The mechanism of betaine action appeared to be via the methylation reaction catalyzed by betaine-homocysteine-methyltransferase. To conclude, our results indicate that the elevation of S-adenosylhomocysteine levels in the liver by ethanol is a major factor in altering methylation reactions and in increasing apoptosis in the liver. We conclude that ethanol-induced alteration in methionine metabolic pathways may play a crucial role in the pathologies associated with alcoholic liver injury and that betaine administration may have beneficial therapeutic effects.

  1. The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats.

    Science.gov (United States)

    Willcocks, Andrea L; McNally, Gavan P

    2013-01-01

    The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation.

  2. Role of Neurexin-1β and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats

    Science.gov (United States)

    Shen, Haitao; Chen, Zhouqing; Wang, Yang; Gao, Anju; Li, Haiying; Cui, Yonghua; Zhang, Li; Xu, Xiang; Wang, Zhong

    2015-01-01

    Background and Purpose— Neurexin-1β and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1β and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction. Methods— In vivo, 228 Sprague–Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1β and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1β and neuroligin-1, as well as neurological outcome. Results— Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1β and neuroligin-1 and the interaction between neurexin-1β and neuroligin-1 in neurons. In addition, the interaction between neurexin-1β and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1β and neuroligin-1 and aggravated by the knockdown of neurexin-1β and neuroligin-1. More importantly, neurexin-1β and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1β and neuroligin-1 knockdown induced an opposite effect. Conclusions— Enhancing the expressions of neurexin-1β and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1β and neuroligin-1 might be good targets for improving cognitive function after SAH. PMID:26219651

  3. Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation.

    Science.gov (United States)

    Ghosh, S S; Massey, H D; Krieg, R; Fazelbhoy, Z A; Ghosh, S; Sica, D A; Fakhry, I; Gehr, T W B

    2009-05-01

    TNF-alpha and NF-kappaB play important roles in the development of inflammation in chronic renal failure (CRF). In hepatic cells, curcumin is shown to antagonize TNF-alpha-elicited NF-kappaB activation. In this study, we hypothesized that if inflammation plays a key role in renal failure then curcumin should be effective in improving CRF. The effectiveness of curcumin was compared with enalapril, a compound known to ameliorate human and experimental CRF. Investigation was conducted in Sprague-Dawley rats where CRF was induced by 5/6 nephrectomy (Nx). The Nx animals were divided into untreated (Nx), curcumin-treated (curcumin), and enalapril-treated (enalapril) groups. Sham-operated animals served as a control. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was significantly reduced by curcumin and enalapril treatment. However, only enalapril significantly improved blood pressure. Compared with the control, the Nx animals had significantly higher plasma and kidney TNF-alpha, which was associated with NF-kappaB activation and macrophage infiltration in the kidney. These changes were effectively antagonized by curcumin and enalapril treatment. The decline in the anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARgamma) seen in Nx animals was also counteracted by curcumin and enalapril. Studies in mesangial cells were carried out to further establish that the anti-inflammatory effect of curcumin in vivo was mediated essentially by antagonizing TNF-alpha. Curcumin dose dependently antagonized the TNF-alpha-mediated decrease in PPARgamma and blocked transactivation of NF-kappaB and repression of PPARgamma, indicating that the anti-inflamatory property of curcumin may be responsible for alleviating CRF in Nx animals.

  4. Role of Kupffer cells in acute hemorrhagic necrotizing pancreatitis-associated lung injury of rats

    Institute of Scientific and Technical Information of China (English)

    Hong-Bin Liu; Nai-Qiang Cui; Dong-Hua Li; Chang Chen

    2006-01-01

    AIM: To investigate the role of Kupffer cells (KCs) in acute hemorrhagic necrotizing pancreatitis-associated lung injury (AHNP-LI).METHODS: Forty-two rats were allocated to four groups [sham operation, AHNP model, gadolinium chloride (GdCl3) pretreatment, GdCl3 control]. In GdCl3pretreatment group, GdCl3 was administered by caudal vein injection 24 h before the AHNP model induction.Blood from the iliac artery, alveolar macrophages and tissues from the pancreas and lung, were collected in six animals per group 3 and 6 h after acute pancreatitis induction. TNF-α, IL-1 of serum, myeloperoxidase (MPO)of lung tissue, NF-κB activation of alveolar macrophages were detected. Serum AST and ALT in sham operation group and GdCl3 control group were tested. In addition,histopathological changes of the pancreas and lung were observed under light microscope.RESULTS: MPO of lung tissue and TNF-α, IL-1 levels of serum were all reduced significantly in GdCl3pretreatment group compared to those in AHNP group(P<0.01). NF-κB activation of alveolar macrophages was also attenuated significantly in GdCl3 pretreatment group compared to that in AHNP group (P<0.01). The pathological injury of the lung was ameliorated obviously in GdCl3 pretreatment group compared to that in AHNP group. Nevertheless, the serum amylase level did not reduce and injury of the pancreas was not prevented in GdCl3 pretreatment group.CONCLUSION: Pulmonary injury induced by AHNP is mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCl3 and KCs play a vital role in AHNP-LI.

  5. Role of IKK/NF-κB signaling in extinction of conditioned place aversion memory in rats.

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    Cheng-Hao Yang

    Full Text Available The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v. selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction.

  6. Projections from Orbitofrontal Cortex to Anterior Piriform Cortex in the Rat Suggest a Role in Olfactory Information Processing

    OpenAIRE

    ILLIG, KURT R.

    2005-01-01

    The orbitofrontal cortex (OFC) has been characterized as a higher-order, multimodal sensory cortex. Evidence from electrophysiological and behavioral studies in the rat has suggested that OFC plays a role in modulating olfactory guided behavior, and a significant projection to OFC arises from piriform cortex, the traditional primary olfactory cortex. To discern how OFC interacts with primary olfactory structures, the anterograde tracer Phaseolus vulgaris leucoagglutinin was injected into orbi...

  7. Enacting The Spirit Of The United Nations Convention On The Rights Of Persons With Disabilities: The Role Of Postsecondary Faculty In Ensuring Access

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    Irene M. Duranczyk

    2013-11-01

    Full Text Available Nations throughout the world have signed the United Nations (UN Convention on the Rights of Persons With Disabilities.  Many postsecondary educators support the ideals of access and equity for students with disabilities, but have received no training in how to ensure that these goals are achieved.  This paper introduces the concepts of universal design and universal instructional design and provides specific guidelines for general communication and for creating accessible classrooms, lectures or presentations, documents, media, websites, and distance education courses.

  8. Ethanol-induced social facilitation in adolescent rats: role of endogenous activity at mu opioid receptors.

    Science.gov (United States)

    Varlinskaya, Elena I; Spear, Linda P

    2009-06-01

    Ethanol consumption is considerably elevated during adolescence. Attractiveness of alcohol for humans during the adolescent developmental period is based, in part, on its ability to induce social facilitation--a facilitation of social interactions not only evident in human adolescents but also in adolescent rats. Endogenous opioid systems are among the multiple neural systems implicated in the behavioral and reinforcing effects of ethanol and may play a substantial role in modulating stimulatory effects of low doses of ethanol on social behavior during adolescence. This possibility was explored in the present study through the use of an animal model of peer-directed social behavior. Sprague-Dawley rats were challenged early in adolescence with saline or ethanol intraperitoneally (i.p.), placed into an individual holding cage for 30 minutes, and then tested in a familiar situation with a nonmanipulated partner of the same age and sex. In Experiment 1, each test subject was injected subcutaneously with one of the three doses of a nonselective opioid antagonist naloxone (0, 0.05, and 0.1 mg/kg), 5 minutes prior to the social interaction test and 25 minutes following challenge with saline or ethanol (0.5 g/kg), whereas in Experiment 2 animals were challenged with one of the six doses of ethanol (0, 0.25, 0.5, 0.75, 1.0, and 1.25 g/kg) prior to injection of either saline or naloxone (0.05 mg/kg). In Experiment 3, animals were pretreated i.p. with the selective mu-opioid antagonist CTOP (0, 0.01, 0.025, 0.05, and 0.1 mg/kg) 30 minutes prior to challenge with saline or ethanol (0.5 g/kg). Low doses of ethanol (0.5 and 0.75 g/kg) produced social facilitation, as indexed by significant increases in play fighting and social investigation. Both doses of naloxone and the three highest doses of CTOP blocked the stimulatory effects of ethanol on play fighting but not on social investigation. These effects were not associated with alterations in ethanol pharmacokinetic properties

  9. Immunologic role of nitric oxide in acute rejection of golden hamster to rat liver xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    Tong-Jin Diao; Tong-Ye Yuan; You-Lin Li

    2002-01-01

    AIM: To evaluate the immunologic role and expressionsignificances of nitric oxide(NO), nitric oxide synthase(NOS),and its isoenzyme in acute rejection to liverxenografts from golden hamster in rat.METHODS: Liver transplantations were randomlydivided into five groups(n=6-9):isografts (group I );xenografts (groupⅡ); xenografts plus cyclosporinetreatment (group Ⅲ), xenografts pluscyclophosphamide treatment combined withsplenectomy (group Ⅳ), and xenografts usingcyclophosphamide in combination with splenectomy(group Ⅳ) and xenografts using splenectomy inaddition to cyclophosphamide and cyclosporinetreatments(group V) .The levels of ALT, TNF- α, andnitric oxide production(NOx) in serum of reciprentswere examined,and expressions of type Ⅱ (iNOS) andtypeⅢ (cNOS) nitric oxide synthase(NOS)-inducibleNOS(iNOS) and constitutive NOS(cNOS) wereobserved by NADPH diaphorase histochemical andimmunohistochemical staining.RESULTS: The level of serum ALT, activity of serumTNF-α and systemic levels of NO metabolite in groupsⅡand Ⅳ were higher than those of groups Ⅰ andy(serum ALT, 2416±475, 2540±82.5) nkat. L-1 vs(556.8±43.5, 677.30±38.2 ) nkat. L-1, P<0.01;(serum TNF-α, 353.5±16.1,444.6±28.1) ng.L-1 vs38.5±5.2, 52.0±5.7) ng.L-1, P<0.01; (serum NOx514.6 ± 18.1, 336.0 ± 43.0 )nmol.g-1, vs 26.1 ± 5.7, 27.7±6.0) nmol.g-1, P<0.01.Cyclosporine in group Ⅲcan repress the cellular immune response and thesynthesis of nitric oxide and the expression of NOsynthase,but not prolong the liver xenograftsurvival.The over-expression of NOS, iNOS and cNOSin liver xenograft rejection in groups Ⅱand Ⅳ weredetected by NADPH diaphorase histochemical andimmunohistochemical staining.CONCLUSION: The degrees of acute rejection can beeffectively repressed in golden hamster to rat liverxenografts with splenectomy and cyclosporine. Nitricoxide metabolites, and nitric oxide synthase and itsisoenzymes,above all inducible NOS (iNOS) can beused as potential diagnostic

  10. Role of P2 Receptors as Modulators of Rat Eosinophil Recruitment in Allergic Inflammation.

    Science.gov (United States)

    Alberto, Anael Viana Pinto; Faria, Robson Xavier; de Menezes, Joao Ricardo Lacerda; Surrage, Andrea; da Rocha, Natasha Cristina; Ferreira, Leonardo Gomes Braga; Frutuoso, Valber da Silva; Martins, Marco Aurélio; Alves, Luiz Anastácio

    2016-01-01

    ATP and other nucleotides are released from cells through regulated pathways or following the loss of plasma membrane integrity. Once outside the cell, these compounds can activate P2 receptors: P2X ionotropic receptors and G protein-coupled P2Y receptors. Eosinophils represent major effector cells in the allergic inflammatory response and they are, in fact, associated with several physiological and pathological processes. Here we investigate the expression of P2 receptors and roles of those receptors in murine eosinophils. In this context, our first step was to investigate the expression and functionality of the P2X receptors by patch clamping, our results showed a potency ranking order of ATP>ATPγS> 2meSATP> ADP> αβmeATP> βγmeATP>BzATP> UTP> UDP>cAMP. This data suggest the presence of P2X1, P2X2 and P2X7. Next we evaluate by microfluorimetry the expression of P2Y receptors, our results based in the ranking order of potency (UTP>ATPγS> ATP > UDP> ADP >2meSATP > αβmeATP) suggests the presence of P2Y2, P2Y4, P2Y6 and P2Y11. Moreover, we confirmed our findings by immunofluorescence assays. We also did chemotaxis assays to verify whether nucleotides could induce migration. After 1 or 2 hours of incubation, ATP increased migration of eosinophils, as well as ATPγS, a less hydrolysable analogue of ATP, while suramin a P2 blocker abolished migration. In keeping with this idea, we tested whether these receptors are implicated in the migration of eosinophils to an inflammation site in vivo, using a model of rat allergic pleurisy. In fact, migration of eosinophils has increased when ATP or ATPγS were applied in the pleural cavity, and once more suramin blocked this effect. We have demonstrated that rat eosinophils express P2X and P2Y receptors. In addition, the activation of P2 receptors can increase migration of eosinophils in vitro and in vivo, an effect blocked by suramin.

  11. A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells.

    Science.gov (United States)

    Li, Li; Zhu, Jing; Tian, Jie; Liu, Xiaoyan; Feng, Chuan

    2010-12-01

    MSCs possess the capacity of self-renewal and potential of differentiation into various kinds of specialized tissue cells including myocardiocytes. From self-renewing to oriented differentiation, chromatin is remodeled into heritable states that allow activation or maintain the repression of regulatory genes, which means specific genes in self-renewing switched off and specific genes in oriented differentiation activated (Bernstein et al. Cell 125:315-326, 2006). These epigenetic states are established and controlled largely by specific patterns of histone posttranslational modifications, in particular, histone acetylation (Li Nat Rev Genet 3:662-673, 2002). In cardiomyocyte differentiation of rat MSCs, we focused on Gcn5, which linked a known transcriptional coactivator with catalytic histone acetyltransferase activity (Brownell et al. Cell 84:843-851, 1996). To clarify participatory in vivo role of Gcn5, using an RNA interference (RNAi) strategy employing shRNA to specifically knockdown Gcn5 expression in MSCs, we found that HAT activity altered dynamically depended on the inhibition of Gcn5 during MSCs differentiation. Chromatin immunoprecipitation (ChIP) assay showed the increased binding of acetyl histone H3 to the early cardiomyocyte-specific genes GATA4 and NKx2.5 promoters in cardiomyocyte differentiation of MSCs by 5-azacytidine inducing, whereas the decreased binding with lower Gcn5 expression. Cell ultrastructure analysis revealed that MSCs induced by 5-azacytidine possess morphological characteristics of cardiomyocyte cells. The shape of MSCs transfected by Gcn5 RNAi was similar to normal MSCs, but the chromatin showed heavy electron-density and a hard-packed structure. This intermediate state of chromatin may be an inactive part of MSCs differentiation. These results demonstrate that Gcn5, possessing acetyltransferase activity, is involved in regulating chromatin configuration around GATA4 and NKx2.5 in cardiomyocyte differentiation of rat MSCs by

  12. Role of P2 Receptors as Modulators of Rat Eosinophil Recruitment in Allergic Inflammation.

    Directory of Open Access Journals (Sweden)

    Anael Viana Pinto Alberto

    Full Text Available ATP and other nucleotides are released from cells through regulated pathways or following the loss of plasma membrane integrity. Once outside the cell, these compounds can activate P2 receptors: P2X ionotropic receptors and G protein-coupled P2Y receptors. Eosinophils represent major effector cells in the allergic inflammatory response and they are, in fact, associated with several physiological and pathological processes. Here we investigate the expression of P2 receptors and roles of those receptors in murine eosinophils. In this context, our first step was to investigate the expression and functionality of the P2X receptors by patch clamping, our results showed a potency ranking order of ATP>ATPγS> 2meSATP> ADP> αβmeATP> βγmeATP>BzATP> UTP> UDP>cAMP. This data suggest the presence of P2X1, P2X2 and P2X7. Next we evaluate by microfluorimetry the expression of P2Y receptors, our results based in the ranking order of potency (UTP>ATPγS> ATP > UDP> ADP >2meSATP > αβmeATP suggests the presence of P2Y2, P2Y4, P2Y6 and P2Y11. Moreover, we confirmed our findings by immunofluorescence assays. We also did chemotaxis assays to verify whether nucleotides could induce migration. After 1 or 2 hours of incubation, ATP increased migration of eosinophils, as well as ATPγS, a less hydrolysable analogue of ATP, while suramin a P2 blocker abolished migration. In keeping with this idea, we tested whether these receptors are implicated in the migration of eosinophils to an inflammation site in vivo, using a model of rat allergic pleurisy. In fact, migration of eosinophils has increased when ATP or ATPγS were applied in the pleural cavity, and once more suramin blocked this effect. We have demonstrated that rat eosinophils express P2X and P2Y receptors. In addition, the activation of P2 receptors can increase migration of eosinophils in vitro and in vivo, an effect blocked by suramin.

  13. Evidence supporting a role for mammalian chitinases in efficacy of caspofungin against experimental aspergillosis in immunocompromised rats.

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    Patricia E B Verwer

    Full Text Available OBJECTIVES: Caspofungin, currently used as salvage therapy for invasive pulmonary aspergillosis (IPA, strangely only causes morphological changes in fungal growth in vitro but does not inhibit the growth. In vivo it has good efficacy. Therefore the question arises how this in vivo activity is reached. Caspofungin is known to increase the amount of chitin in the fungal cell wall. Mammals produce two chitinases, chitotriosidase and AMCase, which can hydrolyse chitin. We hypothesized that the mammalian chitinases play a role in the in vivo efficacy of caspofungin. METHODS: In order to determine the role of chitotriosidase and AMCase in IPA, both chitinases were measured in rats which did or did not receive caspofungin treatment. In order to understand the role of each chitinase in the breakdown of the caspofungin-exposed cells, we also exposed caspofungin treated fungi to recombinant enzymes in vitro. RESULTS: IPA in immunocompromised rats caused a dramatic increase in chitinase activity. This increase in chitinase activity was still noted when rats were treated with caspofungin. In vitro, it was demonstrated that the action of both chitinases were needed to lyse the fungal cell wall upon caspofungin exposure. CONCLUSION: Caspofungin seemed to alter the cell wall in such a way that the two chitinases, when combined, could lyse the fungal cell wall and assisted in clearing the fungal pathogen. We also found that both chitinases combined had a direct effect on the fungus in vitro.

  14. Modulatory role of sensory innervation on hair follicle stem cell progeny during wound healing of the rat skin.

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    Eduardo Martínez-Martínez

    Full Text Available BACKGROUND: The bulge region of the hair follicle contains resident epithelial stem cells (SCs that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. METHODOLOGY/PRINCIPAL FINDINGS: We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+ nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+ nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+/CldU(+. The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+/CldU(+ cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP and calcitonin gene-related peptide (CGRP receptor immunoreactivity were both present in CD34(+ and BrdU-retaining cells of the hair follicles. CONCLUSIONS/SIGNIFICANCE: Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-04-01

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

  16. Role of sex hormones in hypercapnia-induced activation of the locus coeruleus in female and male rats.

    Science.gov (United States)

    de Carvalho, D; Marques, D A; Bernuci, M P; Leite, C M; Araújo-Lopes, R; Anselmo-Franci, J; Bícego, K C; Szawka, R E; Gargaglioni, L H

    2016-01-28

    The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Most of the studies involving the role of the LC in hypercapnic ventilatory responses have been performed in males. Since ovarian steroids modulate the activity of LC neurons and females have a different respiratory response to CO2 than males, we evaluated the activity of LC noradrenergic neurons during normocapnia and hypercapnia in female and male rats with distinct sex hormone levels. Ovariectomized (OVX), estradiol (E2)-treated ovariectomized (OVX+E2) and female rats on the diestrous day of the estrous cycle were evaluated. Concurrently, males were investigated as gonad-intact, orchidectomized (ORX), testosterone (T)-treated ORX (ORX+T), and E2-treated ORX (ORX+E2). Activation of LC neurons was determined by double-label immunohistochemistry to c-Fos and tyrosine hydroxylase (TH). Hypercapnia induced by 7% CO2 increased the number of c-Fos/TH-immunoreactive (ir) neurons in the LC of all groups when compared to air exposure. Hypercapnia-induced c-Fos expression did not differ between diestrous females and intact male rats. In the OVX+E2 group, there was attenuation in the c-Fos expression during normocapnia compared with OVX rats, but CO2 responsiveness was not altered. Moreover, in ORX rats, neither T nor E2 treatments changed c-Fos expression in LC noradrenergic neurons. Thus, in female rats, E2 reduces activation of LC noradrenergic neurons, whereas in males, sex hormones do not influence the LC activity.

  17. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Directory of Open Access Journals (Sweden)

    María F Albertoni Borghese

    Full Text Available Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day, a dual endothelin receptor antagonist (ERA. The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  18. Nonpreventive role of aerobic exercise against cisplatin-induced nephrotoxicity in female rats

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    Jalaledin Noroozi

    2015-01-01

    Conclusions: Aerobic exercise cannot reduce CP-induced nephrotoxicity in female rats. Increasing the damage in female rats may be related to female sex hormone estrogen or gender differences in renal hemodynamic and renin-angiotensin system activity in the presence of exercise. In general, it is recommended that the females under CP chemotherapy avoid exercising during treatment.

  19. Sildenafil-mediated neovascularization and protection against myocardial ischaemia reperfusion injury in rats: role of VEGF/angiopoietin-1

    Science.gov (United States)

    Koneru, Srikanth; Varma Penumathsa, Suresh; Thirunavukkarasu, Mahesh; Vidavalur, Ramesh; Zhan, Lijun; Singal, Pawan K; Engelman, Richard M; Das, Dipak K; Maulik, Nilanjana

    2008-01-01

    Sildenafil citrate (SC), a drug for erectile dysfunction, is now emerging as a cardiopulmonary drug. Our study aimed to determine a novel role of sildenafil on cardioprotection through stimulating angiogenesis during ischaemia (I) reperfusion (R) at both capillary and arteriolar levels and to examine the role of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in this mechanistic effect. Rats were divided into: control sham (CS), sildenafil sham (SS), control + IR (CIR) and sildenafil + IR (SIR). Rats were given 0.7 mg/kg, (i.v) of SC or saline 30 min. before occlusion of left anterior descending artery followed by reperfusion (R). Sildenafil treatment increased capillary and arteriolar density followed by increased blood flow (2-fold) compared to control. Treatment with sildenafil demonstrated increased VEGF and Ang-1 mRNA after early reperfusion. PCR data were validated by Western blot analysis. Significant reduction in infarct size, cardiomyocyte and endothelial apoptosis were observed in SC-treated rats. Increased phosphorylation of Akt, eNOS and expression of anti-apoptotic protein Bcl-2, and thioredoxin, hemeoxygenase-1 were observed in SC-treated rats. Echocardiography demonstrated increased fractional shortening and ejection fraction following 45 days of reperfusion in the treatment group. Stress testing with dobutamine infusion and echocardiogram revealed increased contractile reserve in the treatment group. Our study demonstrated for the first time a strong additional therapeutic potential of sildenafil by up-regulating VEGF and Ang-1 system, probably by stimulating a cascade of events leading to neovascularization and conferring myocardial protection in in vivo I/R rat model. PMID:18373738

  20. Change and role of heme oxygenase-1 in injured lungs following limb ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    周君琳; 朱晓光; 林源; 凌亦凌; 邵新中; 张桂生

    2004-01-01

    Objective: To study the change and role of hemeoxygenase-1 (HO-1) in injured lungs following limbischemia/reperfusion in rats.Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8,16 and 24 hours(n =8 in each time point)was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats.And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion,among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion.And the animal mortality was observed on the other 24rats.Results: Northern blotting analysis showed that HO-1mRNA increased significantly at 4 hours after reperfusion,peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO

  1. The Hague Judgments Convention

    DEFF Research Database (Denmark)

    Nielsen, Peter Arnt

    2011-01-01

    The Hague Judgments Convention of 2005 is the first global convention on international jurisdiction and recognition and enforcement of judgments in civil and commercial matters. The author explains the political and legal background of the Convention, its content and certain crucial issues during...

  2. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  3. Role of Shenfu Injection (参附注射液) in Rats with Systemic Inflammatory Response Syndrome

    Institute of Scientific and Technical Information of China (English)

    WANG Jin; QIAO Li-fen; YANG Guang-tian

    2008-01-01

    Objective: To investigate the role of Shenfu Injection (参附注射液SFI) in rats with systemic inflammatory response syndrome (SIRS). Methods: The SIRS rat model was induced by the intravenous injection of lipopolysaccharide (LPS). Forty-five male Wistar rats were randomly divided into 3 groups, the sham operative control group (control group, n=5), the SIRS model group (model group, n=20) and the SFI treatment group (SFI group, n=20). LPS was injected through the external jugular vein (12 mg/kg, 6 mg/mL) to all rats except for those in the control group, and SFI (10 mL/kg) was given to those in the SF group only once through intraperitoneal injection, while the normal saline (10 mL/kg) was given to those in the model group. For those in the control group, normal saline was given through the external jugular vein (2 mL/kg) and intraperitoneal injection (10 mL/kg). Then, rats in the model group and SFI group were divided into 4 subgroups according to the time points, i.e., 1 h, 2 h, 4 h and 6 h subgroups, 5 rats in each group. The activity of nuclear factor of κ B(NF-κ B) of in blood mononuclear cells and the plasma levels of tumor necrosis factor-α (TNF-α) nd interleukin 6-(IL-6) were determined using enzyme-linked immunoabsordent assay (ELISA) at 1 h, 2 h, 4 h and 6 h after modeling. Histopathologic changes of the lung and liver were observed under a light microscope. Results: Compared with the control group, the activity of NF- κ B in mononuclear cells and the plasma level of TNF-α were obviously increased at each time points (all P<0.01), reaching the peaks at 2 h after modeling. The plasma level of IL-6 increased gradually as time went by in the model group (P<0.01). Pathological examination showed pulmonary alveoli hemorrhage, edema and inflammatory cell infiltration in the lung tissue, and angiotelectasis, congestion, and local necrosis in the liver tissue in the model group. Compared with the model group, the activity of NF- κ B and the levels of

  4. Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats.

    Science.gov (United States)

    Manduca, Antonia; Morena, Maria; Campolongo, Patrizia; Servadio, Michela; Palmery, Maura; Trabace, Luigia; Hill, Matthew N; Vanderschuren, Louk J M J; Cuomo, Vincenzo; Trezza, Viviana

    2015-08-01

    To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats. JZL195, administered at the dose of 0.01mg/kg, increased social play behavior, that is the most characteristic social activity displayed by adolescent rats, and increased social interaction in adult animals. At both ages, these behavioral effects were antagonized by the CB1 cannabinoid receptor antagonist SR141716A and were associated with increased brain levels of 2-AG, but not AEA. Conversely, at the dose of 1mg/kg, JZL195 decreased general social exploration in adolescent rats without affecting social play behavior, and induced anxiogenic-like effects in the elevated plus-maze test both in adolescent and adult animals. These effects, mediated by activation of CB1 cannabinoid receptors, were paralleled by simultaneous increase in AEA and 2-AG levels in adolescent rats, and by an increase of only 2-AG levels in adult animals. These findings provide the first evidence for a role of 2-AG in social behavior, highlight the different contributions of AEA and 2-AG in the modulation of emotionality at different developmental ages and suggest that pharmacological inhibition of AEA and 2-AG hydrolysis is a useful approach to investigate the role of these endocannabinoids in neurobehavioral processes.

  5. Role of commensal bacteria in chronic experimental colitis: lessons from the HLA-B27 transgenic rat.

    Science.gov (United States)

    Rath, Heiko C

    Rats on Lewis or Fischer background, transgenic for human HLA-B27 and beta(2)-microglobulin genes spontaneously develop colitis, gastritis, arthritis, dermatitis, orchitis, epididymitis, carditis, alopecia and nail changes. Disease susceptibility correlates with the gene copy number and is influenced by the genetic background. The pathomechanism in this model is still not completely understood. Cell transfer experiments indicate an essential role of HLA-B27 expression in bone marrow-derived cells. On Fischer background the onset of colitis occurs at 2 months of age, peaks at 3 months of age, and plateaus. Histologic findings include inflammatory cell infiltration, mostly limited to the mucosa, crypt hyperplasia, reduction of goblet cells, occasionally crypt abscesses and early ulcers. There is evidence that normal luminal bacteria play an essential role in initiating and perpetuating chronic colitis and gastritis in HLA-B27 transgenic rats: Transgenic rats raised under germ-free conditions do not develop gastrointestinal disease, whereas transgenic littermates exposed to specific pathogen-free bacteria develop colitis and gastritis within 2-4 weeks. Obligate anaerobic bacteria, especially Bacteroides spp., may play a predominant role since metronidazole prevents colitis and transgenic germ-free rats contaminated with a cocktail of six obligate and facultative anaerobic bacteria develop colitis and gastritis only in the presence of Bacteroides vulgatus. Luminal bacteria may also be involved in trafficking and homing of inflammatory cells into remote organs, since varying cecal bacterial composition does not only alter local inflammation but also influences gastritis. Lymphocyte transfer experiments indicate a specific response to luminal bacteria. In summary, this animal model is suitable for investigating the influence of normal luminal bacteria on the cellular immune mechanism in chronic intestinal inflammation.

  6. Effect of electromagnetic waves from mobile phone on immune status of male rats: possible protective role of vitamin D.

    Science.gov (United States)

    El-Gohary, Ola Ahmed; Said, Mona Abdel-Azeem

    2017-02-01

    There are considerable public concerns about the relationship between mobile phone radiation and human health. The present study assesses the effect of electromagnetic field (EMF) emitted from a mobile phone on the immune system in rats and the possible protective role of vitamin D. Rats were randomly divided into six groups: Group I: control group; Group II: received vitamin D (1000 IU/kg/day) orally; Group III: exposed to EMF 1 h/day; Group IV: exposed to EMF 2 h/day; Group V: exposed to EMF 1 h/day and received vitamin D (1000 IU/kg/day); Group VI: exposed to EMF 2 h/day and received vitamin D (1000 IU/kg/day). After 30 days of exposure time, 1 h/day EMF exposure resulted in significant decrease in immunoglobulin levels (IgA, IgE, IgM, and IgG); total leukocyte, lymphocyte, eosinophil and basophil counts; and a significant increase in neutrophil and monocyte counts. These changes were more increased in the group exposed to 2 h/day EMF. Vitamin D supplementation in EMF-exposed rats reversed these results when compared with EMF-exposed groups. In contrast, 7, 14, and 21 days of EMF exposure produced nonsignificant differences in these parameters among all experimental groups. We concluded that exposure to mobile phone radiation compromises the immune system of rats, and vitamin D appears to have a protective effect.

  7. Protective role of turmeric on histological, ultrastructural and serobiochemical changes in cisplatin-induced nephrotoxicity in female rats

    Directory of Open Access Journals (Sweden)

    B. Ramya

    2013-10-01

    Full Text Available Aim: Protective role of turmeric was assessed against cisplatin-induced histological and ultra-structural changes in kidney.Materials and Methods: A total of 48 rats were divided into 4 groups of 12 rats in each. Group 1 was kept as sham control,group 2 was treated with cisplatin (@ 2 mg/kg b.wt, intraperitoneally on day 1, 7, 14 and 21, group 3 with turmeric (@ 0.05mg/kg b.wt. p.o. once daily for 28 days and group 4 with cisplatin + turmeric (as per above schedule. Blood was collected atfortnight intervals and serum was separated for estimation of kidney biomarkers. Six rats in each group were then euthanizedon day 14 and 28 for histopathology, and tissue parameters were assayed on day 28.Results: Thibarbituric acid reacting substances (TBARS, protein carbonyls, serum creatinine, blood urea nitrogen (BUNwere significantly (P < 0.05 increased, while GSH was significantly (P < 0.05 decreased in group 2 as compared to othergroups. Histological sections of kidney from group 2 rats showed marked inter-tubular haemorrhages, congestion, markeddilation of tubules, and other lesions of pathological significance. Ultrastructural changes of pathological significance werealso recorded in group 2. Kidney sections of group 4 showed nucleus with uniform size with well differentiated nuclearmembrane and nucleolus, and prominent inter tubular and inter cellular junctions.Conclusion: The study revealed that cisplatin induces nephrotoxicity due to oxidative stress and turmeric was foundbeneficial in countering the adverse effects.

  8. The protective role of bee honey against the toxic effect of melamine in the male rat kidney.

    Science.gov (United States)

    Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Solamy, Suad M

    2015-06-01

    This study aimed to test the protective role of natural bee honey against melamine toxicity in the kidney of male albino rats. The dietary supplementation of melamine at a dose of 20,000 ppm for 28 days induced renal dysfunction, as reflected by a significant increase in kidney function parameters (urea, creatinine, and uric acid) and an increase in potassium levels. In addition, a decrease in catalase and glutathione-S-transferase and an increase in lipid peroxide in the kidney tissue homogenate were also observed. Histological changes in the melamine-treated group revealed hyperplasia and damage in kidney cells and the accumulation of melamine crystals in kidney tissues. Honey treatment for 28 days in rats concurrently administered melamine at a dose of 2.5 g/kg body weight for 28 days improved the kidney function, increased antioxidant enzymes, and decreased lipid peroxide levels. The morphology of the kidney cells of the melamine-fed rats was also improved as a result of honey treatment. In conclusion, this study revealed that natural bee honey protects the kidney against the adverse effects induced by melamine toxicity in male albino rats. © The Author(s) 2014.

  9. Protective Role of Ficus carica Stem Extract against Hepatic Oxidative Damage Induced by Methanol in Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Mongi Saoudi

    2012-01-01

    Full Text Available The present study was aimed to investigate the antioxidant activity of Ficus carica stem extract (FE in methanol-induced hepatotoxicity in male Wistar rats. The rats were divided into two batches: 16 control rats (C drinking tap water and 16 treated rats drinking Ficus carica stem extract for six weeks. Then, each group was divided into two subgroups, and one of them was intraperitoneally injected (i.p. daily methanol at a dose of 2.37 g/kg body weight i.p. for 30 days, for four weeks. The results showed that FE was found to contain large amounts of polyphenols and carotenoids. The treatment with methanol exhibited a significant increase of serum hepatic biochemical parameters (ALT, AST, ALP, and LDH and hepatic lipid peroxidation. Hepatic antioxidant enzymes, namely, SOD, CAT, and GSH-Px, were significantly decreased in methanol-treated animals. FE treatment prior to methanol intoxication has significant role in protecting animals from methanol-induced hepatic oxidative damage.

  10. Role of Mas receptor in renal blood flow response to angiotensin-(1-7 in ovariectomized estradiol treated rats

    Directory of Open Access Journals (Sweden)

    Shadan Saberi

    2016-01-01

    Full Text Available The angiotensin 1-7 (Ang 1-7, is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV female rats. OV female Wistar-rats received estradiol (500 μg/kg/week or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF, and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (P dose <0.001 and A779-treated (P dose<0.01 animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05. When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

  11. The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

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    Hamed Shafaroodi

    2017-02-01

    Full Text Available  Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA, and the activities of catalase (CAT, glutathione peroxidase (GSHPx and superoxide dismutase (SOD have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with L-NAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats.

  12. Effect of verapamil on nitric oxide synthase in a portal vein-ligated rat model: Role of prostaglandin

    Institute of Scientific and Technical Information of China (English)

    Chii-Shyan Lay; CMY May; Fa-Yauh Lee; Yang-Te Tsai; Shou-Dong Lee; Shu Chien; Shlomoh Sinchon

    2006-01-01

    AIM: To investigate the effects of verapamil on nitric oxide (NO) synthesis in a portal vein-ligated rat model.METHODS: Systemic and splanchnic hemodynamics were measured by radiolabeled microspheres in portal hypertensive rats after acute administration of verapamil (2 mg/kg) on chronic treatment with Nw-nitro-L-arginine (NNA)(80 mg/kg) and/or indomethacin (2 mg/kg) .RESULTS: Verapamil (2 mg/kg) caused a marked fall in both arterial pressure and cardiac output accompanied by an insignificant change in the portal pressure and no change in portal venous inflow. This result suggested that verapamil did not cause a reduction in portal vascular resistance of portal hypertensive rats, which was similar between Nw- nitro-L-arginine-treated and indomethacin-treated groups.CONCLUSION: In portal hypertensive rats.pretreated with NNA and/or indomethacin, acute verapamil administration can not reduce the portal pressure,suggesting that NO and prostaglandin play an important role in the pathogenesis of splanchnic arterial vasodilation in portal hypertension.

  13. The role of EGFR/ERK/ELK-1 MAP kinase pathway in the underlying damage to diabetic rat skin

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    Xinhong Ge

    2013-01-01

    Full Text Available Background: Diabetes mellitus (DM is a highly prevalent disease. Atrophy and spontaneous ulcers are the most common cutaneous manifestation of diabetic dermopathy (DD. Before spontaneous ulcers, we believe there is an underlying damage stage although the mechanism is unknown. Aims: To explore the expression of extracellular signal-regulated kinase1/2 (ERK1/2, its correlated upstream protein epidermal growth factor receptor (EGFR and its downstream transcription factor E twenty-six (ETS-like 1(ELK-1in the damage of the diabetic rat skin, and to explore the role of ERK1/2 on the recessive damage to diabetic rat skin. Materials and Methods: Eighty Sprague-Dawley (SD rats weighing 260-300 g were randomly divided into control and streptozotocin (STZ-induced diabetes groups. After 0.5, 2, 4, and 8 weeks, the shaved skin specimens from the back of rats in both groups were collected to observe the histological characteristics of the skin, to measure the thickness of the epidermis and the dermis, and to observe the ultrastructure. Immunohistochemistry (IHC and Western blot techniques were used to detect the expression and activation of ERK1/2, EGFR, ELK-1 in the skin of the rats. Results: There are ultrastructural changes in the DM skin. With the continuance of the diabetes course, the thicknesses of the epidermis and dermis decreased, and the expression of phospho-ERK1/2 (P-ERK1/2, EGFR, and ELK-1 was decreased gradually in the back skin of the diabetes rats. It was significantly lower in 4 and 8 week DM than that of the normal control ( P < 0.05. The expression of P-EGFR and P-ERK1/2 in the back skin of the diabetes rats was positively correlated ( r = 0.572 P < 0.05, and the positive correlation was also obtained between P-ERK1/2 and P-ELK-1 ( r = 0.715, P < 0.05. Conclusion: The phenomenon of recessive damage exists in the skin of diabetes rats, which probably may relate to the weakness of the signal transduction: P-EGFR → ERK1/2 → ELK-1.

  14. Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

    Science.gov (United States)

    Kutlu, O; Karaguzel, E; Gurgen, S G; Okatan, A E; Kutlu, S; Bayraktar, C; Kazaz, I O; Eren, H

    2016-05-01

    We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions.

  15. Antihypertensive responses elicited by central moxonidine in rats: possible role of nitric oxide.

    Science.gov (United States)

    Moreira, Thiago Santos; Takakura, Ana Carolina Thomaz; Sato, Monica Akemi; Menani, José Vanderlei; Colombari, Eduardo

    2006-06-01

    In the present study, we investigated the effects of pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) injected intravenously (IV) on the hypotension, bradycardia, and vasodilation produced by moxonidine (alpha2-adrenergic/imidazoline receptor agonist) injected into the fourth brain ventricle (4th V) in rats submitted to acute hypertension that results from baroreflex blockade by bilateral injections of kynurenic acid (kyn, glutamatergic receptor antagonist) into the nucleus of the solitary tract (NTS) or in normotensive rats. Male Wistar rats (n=5 to 7/group) anesthetized with IV urethane (1.0 g kg(-1) of body weight) and alpha-chloralose (60 mg kg(-1) of body weight) were used. Bilateral injections of kyn (2.7 nmol 100 nL(-1)) into the NTS increased baseline mean arterial pressure (148 +/- 11 mm Hg, vs. control: 102 +/- 4 mm Hg) and baseline heart rate (417 +/- 11 bpm, vs. control: 379 +/- 6 bpm). Moxonidine (20 nmol microL(-1)) into the 4th V reduced mean arterial pressure and heart rate to similar levels in rats treated with kyn into the NTS (68 +/- 9 mm Hg and 359 +/- 7 bpm) or in control normotensive rats (66 +/- 7 mm Hg and 362 +/- 8 bpm, respectively). The pretreatment with L-NAME (25 micromol kg, IV) attenuated the hypotension produced by moxonidine into the 4th V in rats treated with kyn (104 +/- 6 mm Hg) or in normotensive rats (95 +/- 8 mm Hg), without changing bradycardia. Moxonidine into the 4th V also reduced renal, mesenteric, and hindquarter vascular resistances in rats treated or not with kyn into the NTS and the pretreatment with L-NAME IV reduced these effects of moxonidine. Therefore, these data indicate that nitric oxide mechanisms are involved in hypotension and mesenteric, renal, and hindquarter vasodilation induced by central moxonidine in normotensive and in acute hypertensive rats.

  16. Methanol poisoning. VI. Role of folic acid in the production of methanol poisoning in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Makar, A.B. (Alexandria Univ., Egypt); Tephly, T.R.

    1977-05-01

    Methanol poisoning is well known to occur in humans but does not develop in common laboratory animals such as the rat. Rodents display neither metabolic acidosis nor ocular toxicity after methanol treatment, findings that commonly result in humans and that have recently been described in the monkey. Since methanol administration in the monkey leads to marked accumulation of formic acid and metabolic acidosis, experiments were devised to reduce formate metabolism in the rat and thereby study whether methanol administration would lead to the accumulation of formic acid and acidosis in that species. Several methods were employed to induce a state of folate deficiency in the rat, a prerequisite to producing a decrease in formate oxidation to CO/sub 2/ in that species. Rats placed on a folate-deficient diet for 10-12 wk showed a marked decrease in formate oxidation and a marked sensitivity to methanol poisoning, as evidenced by high blood formate levels and marked decreases in blood pH. Treatment of rats with methotrexate was relatively ineffective in inducing decreases in formate oxidation, but in rats fed a folate-deficient diet for 9 days and injected once daily for 9 days with 1 mg/kg methotrexate, a significant elevation of blood formate and decrease in blood pH was observed. In rats that were acidotic following methanol administration no accumulation of formaldehyde was observed. These results indicate that it is possible to sensitize the rat to methanol poisoning by reducing its capacity to oxidize formate. They also show that once the rat is susceptible to methanol poisoning, metabolic acidosis and formate accumulation occur without the accumulation of formaldehyde.

  17. Role of thyroid hormones in the maturation and organisation of rat barrel cortex.

    Science.gov (United States)

    Berbel, P; Ausó, E; García-Velasco, J V; Molina, M L; Camacho, M

    2001-01-01

    The influence of thyroid hormones on cortical development was analysed in rat somatosensory cortex. Maternal and foetal hypothyroidism was induced and maintained by methimazole treatment from embryonic day 13 onwards. 5-Bromo-2'-deoxyuridine (BrdU) labelling in hypothyroid rats showed that cell positioning during corticogenesis followed an inside-out pattern. The radial neurogenetic gradients were more diffuse at all ages with respect to normal rats due to the inappropriate location of many cells, including those of the subcortical white matter. Most (62%) of the cells in the subcortical white matter of hypothyroid rats were labelled at embryonic day 15. Nissl staining of the primary somatosensory cortex showed blurred cortical layer boundaries and an abnormal barrel cytoarchitecture. Cytochrome oxidase and peanut agglutinin staining showed that the tangential organisation of the posteromedial barrel subfield and its layer IV specificity was not lost in hypothyroid rats. However the temporal pattern of peanut agglutinin labelling was delayed 3-4 days with respect to normal rats. In hypothyroid rats, the total barrelfield tangential area was reduced by 27% with respect to normal. The total tangential barrel area, corresponding to peanut agglutinin-negative labelling, occupied 77% of the barrelfield area and only 66% in hypothyroid rats. This reduction was larger with cytochrome oxidase staining where the total barrel area occupied 69% of the barrelfield area in normal and 46% in hypothyroid rats. Our data stress the importance of maternal and foetal thyroid hormones during development, and demonstrate the irreversible effects that maternal and foetal hypothyroidism may have on the intrinsic organisation and maturation of the neocortex.

  18. The preventive role of transurethral antibiotic delivery in a rat model

    Directory of Open Access Journals (Sweden)

    Ozok HU

    2012-07-01

    Full Text Available Hakki U Ozok,1 Okan Ekim,2 Hakan Saltas,3 Ata T Arikok,4 Orkun Babacan,5 Levent Sagnak,1 Hikmet Topaloglu,1 Hamit Ersoy11Department of Urology, 3Department of Microbiology, 4Department of Pathology, Diskapi Yildirim Beyazit Training and Research Hospital, Ministry of Health, Ankara, Turkey; 2Department of Anatomy, 5Department of Microbiology, Ankara University Faculty of Veterinary Medicine, Ankara, TurkeyPurpose: There is currently an emerging need for developing improved approaches for preventing urinary tract infections (UTIs occurring during diagnostic or interventional procedures of the lower urinary tract. We aimed to establish a rat model to assess the use of transurethral antibiotic administration and to provide evidence that this could be used as a preventive therapy.Methods: Animals received fosfomycin trometamol (FOF either urethrally or orally prior to the procedure. A third group was generated as treatment controls and did not receive any medication. Urethral dilation was conducted to recapitulate an interventional procedure prior to intravesical Escherichia coli administration in all three groups. Finally, sham-operated animals were introduced as a fourth group which did not receive antibiotics or E. coli. Colony counts of urine and tissue cultures for the identification of E. coli and histopathological examinations of the bladder and prostate were conducted.Results: Evaluation of infection intensities in cultures as well as histopathological examination of the bladder and prostate demonstrated a preventative role of transurethral FOF administration. In terms of efficiency, local administration of FOF was similar to oral administration.Conclusions: These results suggest that transurethral antibiotic administration is a promising alternative for preventing UTIs occurring during diagnostic or interventional procedures of the lower urinary tract.Keywords: cystitis, fosfomycin, infection, prostatitis, urinary tract

  19. Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2000-01-01

    In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

  20. Role of carnitine palmitoyltransferase I in the control of ketogenesis in primary cultures of rat astrocytes.

    Science.gov (United States)

    Blázquez, C; Sánchez, C; Velasco, G; Guzmán, M

    1998-10-01

    The role of carnitine palmitoyltransferase I (CPT-I) in the control of ketogenesis was studied in primary cultures of rat astrocytes. Ketone bodies were the major product of [14C]palmitate oxidation by cultured astrocytes, whereas CO2 made a minor contribution to the total oxidation products. Using tetradecylglycidate as a specific, cell-permeable inhibitor of CPT-I, a flux control coefficient of 0.77 +/- 0.07 was calculated for CPT-I over the flux of [14C]palmitate to ketone bodies. CPT-I from astrocytes was sensitive to malonyl-CoA (IC50 = 3.4 +/- 0.8 microM) and cross-reacted on western blots with an antibody raised against liver CPT-I. On the other hand, astrocytes expressed significant acetyl-CoA carboxylase (ACC) activity, and consequently they contained considerable amounts of malonyl-CoA. Western blot analysis of ACC isoforms showed that ACC in astrocytes--like in neurons, liver, and white adipose tissue--mostly comprised the 265-kDa isoform, whereas the 280-kDa isoform--which was highly expressed in skeletal muscle--showed much lower abundance. Forskolin was used as a tool to study the modulation of the ketogenic pathway in astrocytes. Thus, forskolin decreased in parallel ACC activity and intracellular malonyl-CoA levels, whereas it stimulated CPT-I activity and [14C]palmitate oxidation to both ketone bodies and CO2. Results show that in cultured astrocytes (a) CPT-I exerts a very high degree of control over ketogenesis from palmitate, (b) the ACC/malonyl-CoA/CPT-I system is similar to that of liver, and (c) the ACC/malonyl-CoA/CPT-I system is subject to regulation by cyclic AMP.

  1. Role of mucus in ischemia/reperfusion-induced gastric mucosal injury in rats.

    Science.gov (United States)

    Mojzis, J; Hegedüsová, R; Mirossay, L

    2000-01-01

    Gastric mucus plays an important role in gastric mucosal protection. Apart from its "barrier" function, it has been demonstrated that mucus protects gastric epithelial cells against toxic oxygen metabolites derived from the xanthine/ xanthine oxidase system. In this study, we investigated the effect of malotilate and sucralfate (mucus production stimulators) and N-acetylcysteine (mucolytic agent) on ischemia/reperfusion-induced gastric mucosal injury. Gastric ischemia was induced by 30 min clamping of the coeliac artery followed by 30 min of reperfusion. The mucus content was determined by the Alcian blue method. Sucralfate (100 mg/kg), malotilate (100 mg/kg), and N-acetylcysteine (100 mg/kg) were given orally 30 min before surgery. Both sucralfate and malotilate increased the mucus production in control rats. On the other hand, N-acetyloysteine significantly decreased mucus content in control (sham) group. A significant decrease of mucus content was found in the control and the N-acetylcysteine pretreated group during the period of ischemia. On the other hand, sucralfate and malotilate prevented the decrease the content of mucus during ischemia. A similar result can be seen after ischemia/reperfusion. In the control group and N-acetylcysteine pretreated group a significant decrease of adherent mucus content was found. However, sucralfate and malotilate increased mucus production (sucralfate significantly). Sucralfate and malotilate also significantly protected the gastric mucosa against ischemia/reperfusion-induced injury. However, N-acetylcysteine significantly increased gastric mucosal injury after ischemia/reperfusion. These results suggest that gastric mucus may be involved in the protection of gastric mucosa after ischemia/reperfusion.

  2. Regulatory roles of bone morphogenetic proteins and glucocorticoids in catecholamine production by rat pheochromocytoma cells.

    Science.gov (United States)

    Kano, Yoshihiro; Otsuka, Fumio; Takeda, Masaya; Suzuki, Jiro; Inagaki, Kenichi; Miyoshi, Tomoko; Miyamoto, Manabu; Otani, Hiroyuki; Ogura, Toshio; Makino, Hirofumi

    2005-12-01

    We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

  3. A role for endothelin in bicuculline-induced neurogenic pulmonary oedema in rats.

    Science.gov (United States)

    Herbst, C; Tippler, B; Shams, H; Simmet, T

    1995-07-01

    1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of seizure-associated pulmonary oedema was examined in mechanically ventilated rats after intravenous bolus injection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2) significantly dropped from 17.49 +/- 1.20 kPa to 7.51 +/- 2.21 kPa (P 0.05) after phosphoramidon pretreatment. In contrast, vehicle-treated animals that received bicuculline showed both significant hypercapnia as well as profound hypoxia. Phosphoramidon significantly diminished the maximum increase in Paw by 76.7 +/- 12.4% (P 0.05) in BQ-123-treated animals. In contrast, vehicle-treated animals that received bicuculline exhibited significant hypercapnia as well as profound hypoxia. BQ-123 significantly reduced the increase in Paw by 51.3 +/- 12.8% (P < 0.01). It affected MABP only slightly and had no effect on the acidosis.6. These results suggest that ET peptides play a significant role in this model of neurogenic pulmonary oedema and may act as mediators of respiratory distress. The deleterious effects of endogenous ET in this model are primarily mediated via the ETA receptor, for they were inhibited by the ETA receptor antagonist, BQ-123. ETA receptor antagonists may therefore be of potential therapeutic value in respiratory distress.

  4. Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins.

    Science.gov (United States)

    Rajesh, Parsanathan; Sathish, Sampath; Srinivasan, Chinnapaiyan; Selvaraj, Jayaraman; Balasubramanian, Karundevi

    2013-03-01

    Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H(2)O(2) and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP-induced changes. It is concluded that DEHP-induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP. Copyright © 2012 Wiley Periodicals, Inc.

  5. Role of oxidative stress in ethanol induced germ cell apoptosis — An experimental study in rats

    OpenAIRE

    Maneesh, M.; Jayalekshmi, H; Dutta, Sanjiba; Chakrabarti, Amit; Vasudevan, D. M.

    2005-01-01

    The study was undertaken to evaluate the possible involvement of oxidative stress in the pathogenesis of ethanol induced testicular atrophy in rats. Adult male rats were orally administered ethanol at a dose of 1.6 g/kg body weight/day for four weeks. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and weighed. Apoptosis was studied by using the Feulgen reaction on 5 μ thin paraffin sections of testis. Testicular homogenate was p...

  6. The kidneys play an important role in the clearance of rFVIIa in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Appa, Rupa S.; Lykkesfeldt, Jens

    2014-01-01

    study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model. MATERIALS AND METHODS: A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance...... of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats. RESULTS: Nephrectomized animals showed stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin was essentially abolished compared...

  7. Indirect role of alpha2-adrenoreceptors in anti-ulcer effect mechanism of nimesulide in rats.

    Science.gov (United States)

    Suleyman, Halis; Halici, Zekai; Cadirci, Elif; Hacimuftuoglu, Ahmet; Keles, Sait; Gocer, Fatma

    2007-05-01

    Nimesulide, a non-steroidal, anti-inflammatory drug, produces ulcerogenic effects in adrenalectomized rats but is gastro-protective in intact rats. The objective of this study was to determine whether adrenal gland hormones are involved in the anti-ulcer effects of nimesulide. The results revealed that 100 mg/kg nimesulide produces gastric ulceration in adrenalectomized rats, which is prevented by prednisolone and adrenaline. The anti-ulcer effects of adrenaline and prednisolone in adrenalectomized rats were in turn antagonized by yohimbine, a selective alpha(2)-receptor blocker, but not by doxazosine (alpha(1)-receptor blocker) or propranolol (beta-blocker). Adrenaline prevented the formation of indomethacin-induced ulcers in both adrenalectomized and intact rats, but prednisolone increased the indomethacin-induced ulcerous area in intact rats, whereas it decreased the size of the ulcers in adrenalectomized rats. In addition, prednisolone prevented ulcer formation in intact rats in which the adrenaline concentration had been decreased by metyrosine. These results suggest that glucocorticoids are anti-ulcerogenic in not only adrenalectomized rats but also in intact rats with diminished circulating levels of adrenaline. In the light of these data, the effect of nimesulide on plasma adrenaline concentrations was studied. In comparison to the adrenaline levels found in intact control rats, the administration of nimesulide at doses of 10, 20, 40 and 100 mg/kg decreased adrenaline concentrations by 12.8, 22.6, 30.4, and 58.2%, respectively, without affecting blood corticosterone concentrations. The anti-ulcer effect of nimesulide was observed to be dose-dependent, and the strength of this effect was directly correlated the decreasing concentration of adrenaline. The concentration of adrenaline was decreased by 60.9% in rats treated with 300 mg/kg metyrosine in which prednisolone produced anti-ulcer effects. In summary, we have shown that nimesulide produces its anti

  8. Beneficial role of ascorbic and folic acids antioxidants against thyroxin-induced testicular dysfunction in hyperthyroid rats.

    Science.gov (United States)

    Beltagy, Doha M; Mohamed, Tarek M; El Said, Ahmed S; Tousson, Ehab

    2016-09-01

    Thyroid hormones play a fundamental role in the regulation of metabolism of almost all mammalian tissue including the reproductive system. Hyperthyroidism in early life may cause delayed sexual maturation, although physical development is normal and skeletal growth may be accelerated. Hyperthyroidism after puberty influences reproductive functions and increases testosterone level. The aim of this work is to study the effect of induced hyperthyroidism by L-thyroxine sodium administration on the testis of rats and to evaluate the ameliorating role of different antioxidants as ascorbic acid and folic acid on the hyperthyroid state via the assessment of different biochemical markers, histopathological and immunochemical sections. DNA analysis of the D1 deiodinase was performed to determine genetic mutation due to hyperthyroidism. The results showed partially disrupted in the measured biochemical parameters and spermatogenesis in hyperthyroid rats. Post-administration of both folic and ascorbic acids together in hyperthyroid rats showed the best ameliorating effects on the thyroid hormones, testosterone, testicular GGT and ALP, and all oxidative stress markers. There is no genetic mutations that occurred in D1 deiodinase due to hyperthyroidism. These findings were indicated by the proliferating cell nuclear antigen (PCNA) studies of testes.

  9. Renal Urotensin II System Plays Roles in the Regulation of Blood Pressure in Dahl Salt-Resistant Rat

    Science.gov (United States)

    Wu, Fei; Chen, Guanjong; Fan, Minhua; Tang, Chaoshu

    2016-01-01

    Introduction. Dahl salt-resistant (SR) animal models are similar to peritoneal dialysis patients with fluid volumes overload with normal blood pressure in hemodynamic profiles. We will verify the roles of UII in the regulation of blood pressure in these animal models. Methodology. The Dahl salt-sensitive (SS) and SR rats and UII receptor gene knocked out (KO) mice were placed on a high-salt diet. Renal tissues were performed for the expression of UII in Dahl groups. Results. After high-salt diet for 6 weeks, the systolic blood pressure (SBP) in SR group was significantly lower, accompanied with higher urinary UII levels, higher 24-hour urinary sodium excretion, and higher urinary creatinine clearance in the SR rats in comparison to SS group. The expressions of UII and UT were both upregulated in the kidney tissues of SR group in comparison to SS group (P < 0.05). After high-salt diet for 8 weeks, the SBP of the KO group is significantly higher than that of the wild type group. Conclusion. We first demonstrate that renal UII system can play important roles in the regulation of blood pressure in Dahl SR rats which can be highly correlated to its effect on renal tubular sodium absorption. PMID:28097020

  10. Role of extracellular signal—regulated kinase in free radical—induced injury in kidney of rats treated with cephaloridine

    Institute of Scientific and Technical Information of China (English)

    GembM; HiraJ

    2002-01-01

    We examined the role of a down stream of intracellular signaling pathway,extracellular signal-regulated kinase(ERK),in cephaloridine (CER)-induced nephrotoxicity in rats.The increase in phosphorylated ERK(pERK,activated ERK) was detected in nucleus fraction prepared from rat kidney cortex 24h after injections of antibiotic CER with the increase in BUN level.The slices prepared from rat kidney cortex were incubated in the medium containing PD980-59,a MEK1/2 inhibitor,for the measurement of free radical production and cell injure(LDH leakage).CER caused not only the increases in lipid peroxidation as an index of free radical production and LDH leakage,but also ERK activation in nucleus fraction.MEK1/2 inhibitor ameliorated CER-induced injury and suppressed ERK activation in the slices.These results suggest a possible role of MEK/ERK signaling pathway in free radical-induced CER nephrotoxicity.

  11. Role of exopolysaccharide in Aggregatibacter actinomycetemcomitans-induced bone resorption in a rat model for periodontal disease.

    Directory of Open Access Journals (Sweden)

    Mayilvahanan Shanmugam

    Full Text Available Aggregatibacter actinomycetemcomitans a causative agent of periodontal disease in humans, forms biofilm on biotic and abiotic surfaces. A. actinomycetemcomitans biofilm is heterogeneous in nature and is composed of proteins, extracellular DNA and exopolysaccharide. To explore the role played by the exopolysaccharide in the colonization and disease progression, we employed genetic reduction approach using our rat model of A. actinomycetemcomitans-induced periodontitis. To this end, a genetically modified strain of A. actinomycetemcomitans lacking the pga operon was compared with the wild-type strain in the rat infection model. The parent and mutant strains were primarily evaluated for bone resorption and disease. Our study showed that colonization, bone resorption/disease and antibody response were all elevated in the wild-type fed rats. The bone resorption/disease caused by the pga mutant strain, lacking the exopolysaccharide, was significantly less (P < 0.05 than the bone resorption/disease caused by the wild-type strain. Further analysis of the expression levels of selected virulence genes through RT-PCR showed that the decrease in colonization, bone resorption and antibody titer in the absence of the exopolysaccharide might be due to attenuated levels of colonization genes, flp-1, apiA and aae in the mutant strain. This study demonstrates that the effect exerted by the exopolysaccharide in A. actinomycetemcomitans-induced bone resorption has hitherto not been recognized and underscores the role played by the exopolysaccharide in A. actinomycetemcomitans-induced disease.

  12. The role of endotoxin in the pathogenesis of gastric mucosal damage in cirrhotic rats with portal hypertensive gastropathy

    Institute of Scientific and Technical Information of China (English)

    ChengLan; XiaoningSun; LiweiDong; BailiHuang; SuYuan; KeliWu

    2011-01-01

    Objective:To study the role and the mechanism of endotoxin in the pathogenesis of gastric mucosa during portal vein hypertension gastrography (PHG) in the rats with cirrhosis. Methods:Rat model for PHG was established by injection of tetrachloride. The animals were injected with endotoxin i.p. at 3 mg/kg and endotoxin antagonist BPI21 i.v. at 2.0 mg/kg. The plasma level of endotoxin as well as the gastric mucosal level of tumor necrosis factor alpha (TNF-α) was measured with azobenzene and ELISA respectively. Furthermore, the pathological changes of the gastric mucosa were studied with HE stainning. Results:In rats with PHG, increased endotoxin and TNF-αas well as the gastric pathological lesion were observed. Injection of endotoxin remarkably increased plasma level of endotoxin as well as the gastric mucosal level of tumor necrosis TNF-αand induced more serious gastric lesion. Animals injected with endotoxin antagonist BPI21 showed improved gastric mucosal lesion, accompanied by the declining TNF-αlevel. Conclusions:Our results suggestes that endotoxin may play a pathogenetic role in PHG by inducing the expression of TNF-α.

  13. Role of zinc as an antioxidant and anti-inflammatory to relieve cadmium oxidative stress induced testicular damage in rats

    Institute of Scientific and Technical Information of China (English)

    Samir Abd El-Monem Bashandy; Enayat Abdel Aziz Omara; Hossam Ebaid; Mohamed Mahmoud Amin; Mahmoud Sanad Soliman

    2016-01-01

    Objective: To investigate the role of zinc in reducing the deleterious effects of cadmium on male gonads. Methods: Rats were injected subcutaneously with CdCl2 and ZnCl2 at dose level of 2.2 mg/kg (1/40 of LD50 of cadmium per day). Results: The rats treated with cadmium exhibited a significant increase in levels of testicular malondialdehyde, tumor necrosis factor-alpha, nitrogen oxide and inducible nitrogen oxide synthase immunostaining reaction, as well as an elevation of blood hydroperoxide and follicle stimulating hormone. In addition, a significant decrease in testicular ascorbic acid, zinc, reduced glutathione, catalase, superoxide dismutase, sex organ weight, plasma testosterone and luteinizing hormone were observed in the cadmium group. Sperm motility and count were decreased with cadmium treatment, while sperm abnormalities elevated significantly. Zinc treatment was found to mitigate the toxic effects of cadmium on oxidative stress, spermatogenesis, sex hormones, and inflammatory markers. Rats injected with cadmium showed intense histopathological changes. Zinc manifested protective role and markedly reduced tissues damage induced by cadmium. Conclusions: The protective effect of zinc can be attributed to its antioxidant and anti-inflammatory properties.

  14. Role of 4-bromophenol and 4-bromocatechol in bromobenzene covalent binding and toxicity in isolated rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Dankovic, D.A.; Billings, R.E.

    1985-06-30

    4-Bromophenol and 4-bromocatechol are formed as metabolites of bromobenzene in vivo and in isolated rat hepatocytes. Both of these metabolites may potentially contribute to the hepatotoxicity of bromobenzene. Bromobenzene metabolism in hepatocytes isolated from phenobarbital-treated rats forms 0.12 to 0.17 mM 4-bromophenol and 4-bromocatechol in 2 hr, with 1 to 3 mM bromobenzene. The role of activated metabolites derived from 4-bromophenol and 4-bromocatechol in bromobenzene covalent binding and toxicity was investigated with isolated hepatocytes in suspension. The covalent binding of the phenol and the catechol was increased four- to eightfold by the addition of unlabeled bromobenzene. Two-hour incubations of 0.25 mM /sup 14/C-labeled 4-bromophenol or 4-bromocatechol with hepatocytes isolated from phenobarbital-treated rats resulted, under these conditions, in no significant toxicity, and approximately 4 and 25%, respectively, of the covalent binding associated with bromobenzene itself. Two- and six-hour incubations with higher 4-bromophenol and 4-bromocatechol concentrations demonstrated that 1 to 3 mM substrate concentrations were required for cytotoxicity. These results show that metabolically produced 4-bromophenol and 4-bromocatechol do not play significant roles in the production of bromobenzene cytotoxicity in isolated hepatocytes, and that they contribute only modestly to bromobenzene covalent binding.

  15. Critical role of matrix metalloproteinase-9 in acute cold exposure-induced stroke in renovascular hypertensive rats.

    Science.gov (United States)

    Li, Chunguang; Li, Xiangpen; Shen, Qingyu; Li, Yi; He, Lei; Li, Mei; Tang, Yamei; Wang, Yidong; He, Qingyu; Peng, Ying

    2013-11-01

    Our objectives are to investigate the role of MMP-9 in cold exposure-induced stroke and assess the preventive effect of doxycycline, a total of 200 rats were assigned to a control group, sham group, 2-kidney, 2-clip (2K-2C) group, and doxycycline-received 2K-2C group (2K-2C+doxy) (N=50, each), and subsequently, each group were randomly assigned to 2 groups: acute cold exposure (ACE) and nonacute cold exposure (NACE) (N=25, each). After the blood pressure was stabilized, rats were maintained on a 12-h light (22°C)/dark (4°C) cycle (ACE group) or a 12-h light (22°C)/dark (22°C) cycle (NACE group) for 3 cycles. The results showed that ACE upregulated Ang II and MMP-9 protein levels in brains and aortas and considerably enhanced stroke incidence in 2K-2C rats. In contrast, doxycycline treatment prevented upregulation of MMP-9 protein expression and activity in brains and aortas in response to ACE and significantly decreased stroke incidence. These findings suggest that cold exposure-induced MMP-9 via activation of RAS might play a critical role in the initiation of cold exposure-induced stroke during chronic hypertension and doxycycline shows protective effects against cold exposure-induced stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors.

    Science.gov (United States)

    Nogueiras, Ruben; Barreiro, M Luz; Caminos, Jorge E; Gaytán, Francisco; Suominen, Janne S; Navarro, Victor M; Casanueva, Felipe F; Aguilar, Enrique; Toppari, Jorma; Diéguez, Carlos; Tena-Sempere, Manuel

    2004-07-01

    Resistin, a recently cloned adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. However, additional metabolic or endocrine functions of this molecule remain largely unexplored. In this study, a series of experiments were undertaken to explore the potential expression, regulation and functional role of this novel adipocytokine in rat testis. Resistin gene expression was demonstrated in rat testis throughout postnatal development, with maximum mRNA levels in adult specimens. At this age, resistin peptide was immunodetected in interstitial Leydig cells and Sertoli cells within seminiferous tubules. Testicular expression of resistin was under hormonal regulation of pituitary gonadotropins and showed stage-specificity, with peak expression values at stages II-VI of the seminiferous epithelial cycle. In addition, testicular resistin mRNA was down-regulated by the selective agonist of PPARgamma, rosiglitazone, in vivo and in vitro. Similarly, fasting and central administration of the adipocyte-derived factor, leptin, evoked a significant reduction in testicular resistin mRNA levels, whereas they remained unaltered in a model of diet-induced obesity. From a functional standpoint, resistin, in a dose-dependent manner, significantly increased both basal and choriogonadotropin-stimulated testosterone secretion in vitro. Overall, our present results provide the first evidence for the expression, regulation and functional role of resistin in rat testis. These data underscore a reproductive facet of this recently cloned molecule, which may operate as a novel endocrine integrator linking energy homeostasis and reproduction.

  17. Role of endothelin-1 antagonist; bosentan, against cisplatin-induced nephrotoxicity in male and female rats

    Directory of Open Access Journals (Sweden)

    Zahra Jokar

    2015-01-01

    Conclusion: Renoprotective effect of BOS, as ET-1 blocker, was not observed against CP-induced nephrotoxicity neither in male nor in female rats. This is while BOS promoted the severity of injuries in females.

  18. ROLE OF NMDA, NICOTINIC, AND GABA RECEPTORS IN THE STEADY STATE VISUAL EVOKED POTENTIAL IN RATS.

    Science.gov (United States)

    This manuscript characterizes the receptor pathways involved in pattern-evoked potential generation in rats" NMDA and nicotinic acetylcholine receptors appear to be involved in the generation of the steady-state pattern evoked response in vivo." The pattern evok...

  19. Role of liver nerves and adrenal medulla in glucose turnover of running rats

    DEFF Research Database (Denmark)

    Sonne, B; Mikines, K J; Richter, Erik;

    1985-01-01

    Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had ident...... and duration, hepatic glycogenolysis and glucose production are not influenced by the autonomic liver nerves but are enhanced by circulating epinephrine....

  20. Deferoxamine prevents cerebral glutathione and vitamin E depletions in asphyxiated neonatal rats: role of body temperature.

    Science.gov (United States)

    Kletkiewicz, Hanna; Nowakowska, Anna; Siejka, Agnieszka; Mila-Kierzenkowska, Celestyna; Woźniak, Alina; Caputa, Michał; Rogalska, Justyna

    2016-01-01

    Hypoxic-ischaemic brain injury involves increased oxidative stress. In asphyxiated newborns iron deposited in the brain catalyses formation of reactive oxygen species. Glutathione (GSH) and vitamin E are key factors protecting cells against such agents. Our previous investigation has demonstrated that newborn rats, showing physiological low body temperature as well as their hyperthermic counterparts injected with deferoxamine (DF) are protected against iron-mediated, delayed neurotoxicity of perinatal asphyxia. Therefore, we decided to study the effects of body temperature and DF on the antioxidant status of the brain in rats exposed neonatally to critical anoxia. Two-day-old newborn rats were exposed to anoxia in 100% nitrogen atmosphere for 10 min. Rectal temperature was kept at 33 °C (physiological to rat neonates), or elevated to the level typical of healthy adult rats (37 °C), or of febrile adult rats (39 °C). Half of the rats exposed to anoxia under extremely hyperthermic conditions (39 °C) were injected with DF. Cerebral concentrations of malondialdehyde (MDA, lipid peroxidation marker) and the levels of GSH and vitamin E were determined post-mortem, (1) immediately after anoxia, (2) 3 days, (3) 7 days, and (4) 2 weeks after anoxia. There were no post-anoxic changes in MDA, GSH and vitamin E concentrations in newborn rats kept at body temperature of 33 °C. In contrast, perinatal anoxia at elevated body temperatures intensified oxidative stress and depleted the antioxidant pool in a temperature-dependent manner. Both the depletion of antioxidants and lipid peroxidation were prevented by post-anoxic DF injection. The data support the idea that hyperthermia may extend perinatal anoxia-induced brain lesions.

  1. Vascular filtration function in galactose-fed versus diabetic rats: The role of polyol pathway activity

    Energy Technology Data Exchange (ETDEWEB)

    Pugliese, G.; Tilton, R.G.; Speedy, A.; Chang, K.; Province, M.A.; Kilo, C.; Williamson, J.R. (Washington Univ. School of Medicine, St Louis, MO (USA))

    1990-07-01

    These studies were undertaken to assess the effects of increased galactose (v increased glucose) metabolism via the polyol pathway on vascular filtration function in the kidneys, eyes, nerves, and aorta. Quantitative radiolabeled tracer techniques were used to assess glomerular filtration rate (GFR) and regional tissue vascular clearance of plasma 131I-bovine serum albumin (BSA) in five groups of male Sprague-Dawley rats: nondiabetic controls, streptozotocin-diabetic rats, nondiabetic rats fed a 50% galactose diet, diabetic rats treated with sorbinil (an aldose reductase inhibitor), and galactose-fed rats treated with sorbinil. Sorbinil was added to the diet to provide a daily dose of approximately .2 mmol/kg body weight. After 2 months of diabetes or galactose ingestion, albumin clearance was increased twofold to fourfold in the eye (anterior uvea, choroid, and retina), sciatic nerve, aorta, and kidney; GFR was increased approximately twofold and urinary excretion of endogenous albumin and IgG were increased approximately 10-fold. Sorbinil treatment markedly reduced or completely prevented all of these changes in galactose-fed, as well as in diabetic rats. These observations support the hypothesis that increased metabolism of glucose via the sorbitol pathway is of central importance in mediating virtually all of the early changes in vascular filtration function associated with diabetes in the kidney, as well as in the eyes, nerves, and aorta. On the other hand, renal hypertrophy in diabetic rats and polyuria, hyperphagia, and impaired weight gain in galactose-fed and in diabetic rats were unaffected by sorbinil and therefore are unlikely to be mediated by increased polyol metabolism.

  2. Lipid peroxidation and oxidative stress in rat erythrocytes induced by aspirin and diazinon:the protective role of selenium

    Institute of Scientific and Technical Information of China (English)

    Abdel-Tawab Halim Mossa; Tarek Mohamed Heikal

    2014-01-01

    Objective:To investigate the adverse effect of exposure to acetylsalicylic acid (ASA), diazinon (DIA) and their combination on oxidant/antioxidant status in rat erythrocytes and the ameliorating role of selenium (Se). Methods: Rats were oral administered ASA at the maximum administration dose (1 350 mg/personal/d=2.5 mg/kg body weight/d), DIA at a dose of 20 mg/kg body weight/d and Se at a dose of 200 µg/kg body weight/d and their combinations for 28 consecutive d. Results: Administration of DIA, ASA and ASA+DIA lead to a significant increment (P≤0.05) in lipid peroxidation as evidenced by the increase in erythrocytes MDA levels by 61.8%, 20.79%and 105.62%, respectively. Co-administration of Se to treated rats modulated the augmentation of MDA levels. Administration of DIA, ASA and ASA+DIA lead to significant decreases (P≤0.05) in the activities of catalase, superoxide dismutase and glutathione peroxidase enzymes when compared to the control group. The most influence and decreases in the activities of the aforementioned enzymes were observed in the treatments of ASA+DIA by 30.53%, 43.42%and 48.31%, respectively. However, co-administration of Se mitigated the significant decreases of superoxide dismutase, catalase and glutathione peroxidase activities to by 14.47%, 15, 36%and 12.29%. Conclusions: It can be concluded that DIA and ASA induced oxidative stress and lipid peroxidation in rat erythrocytes. The results reveal the pronounced ameliorating effect of Se in DIA and ASA intoxicated rats. It is supposed that antioxidant supplementation may be beneficial for the people using ASA for longer periods and exposure to pesticides.

  3. Protective role of quercetin on PCBs-induced oxidative stress and apoptosis in hippocampus of adult rats.

    Science.gov (United States)

    Selvakumar, Kandaswamy; Bavithra, Senthamilselvan; Suganthi, Muralidharan; Benson, Chellakan Selvanesan; Elumalai, Perumal; Arunkumar, Ramachandran; Krishnamoorthy, Gunasekaran; Venkataraman, Prabhu; Arunakaran, Jagadeesan

    2012-04-01

    Polychlorinated biphenyls (PCBs) exposure produces neurodegeneration and induces oxidative stress. Neuroprotective role of quercetin, on PCBs induced apoptosis in hippocampus has not yet been studied. The present study is focused to see whether quercetin supplementation precludes against PCBs induced oxidative stress and hippocampal apoptosis. The results have shown that quercetin at 50 mg/kg bwt/30 days has protected oxidative stress in hippocampus of adult male rats. Quercetin, a free radical scavenger decreased the levels of oxidative stress markers in the hippocampus of simultaneous PCB+quercetin treated rats. The pro-apoptotic and anti-apoptotic molecules such as Bad, Bid, Bax and Bcl2 were altered in the hippocampus of experimental animals. PCBs increased the DNA damage and induced neurodegeneration were assessed by histological studies. PCB induced ROS may be linked to increased hippocampal neuronal apoptosis. Quercetin supplementation decreased the neuronal damage and scavenged the free radicals induced by PCBs and protects PCBs induced apoptosis and oxidative stress.

  4. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response...... that in chemokine-dependent inflammatory responses in lung CC chemokines do not necessarily demonstrate redundant function.......The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES...

  5. The role of calcium in endotoxin-induced release of calcitonin gene-related peptide (CGRP) from rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    唐跃明; 韩启德; 王宪

    1997-01-01

    In the present study, the role of calcium in endotoxin-induced CGRP release was studied. 2 .5-50 μg/mL endotoxin and 1 -10 mmol/L caffeine caused concentration-dependent increase of CGRP release from rat spinal cord in vitro. However, no additive effect could he found when caffeine and endotoxin were concomitantly incubated. By using capsaicin, Ca2+-free medium, Omega-Conotoxin, nifedipine, W-7, ryanodine, MgCl2, Tris-ATP, rutheni-um red, the results indicate that the release of CGRP evoked by endotoxin from the sensory fibers of rat spinal cord is dependent on extracellular calcium. After entering into the cell through the N-type calcium channel, calcium binds to calmodulin, and triggers calcium release from intracellular calcium store by activating the caffeine-sensitive but ryan-odine-insensitive mechanism.

  6. Effects of pregnancy in rats on cysteamine-induced peptic ulcers: role of progesterone.

    Science.gov (United States)

    Montoneri, C; Drago, F

    1997-12-01

    After mating with a sexually active male, groups of female Sprague-Dawley rats were injected with cysteamine (400 mg/kg, subcutaneously) at day 0 (controls), day 5 (early-stage pregnancy), and day 18 (late-stage pregnancy) of pregnancy. In contrast to late-stage pregnancy rats, early-stage pregnancy animals showed a decrease of cysteamine-induced gastroduodenal lesions. When subjected to cysteamine injection, both nonpregnant female and male rats treated for eight days with progesterone (300 microg/rat, subcutaneously) showed a reduced incidence of gastroduodenal lesions. No effect was found in animals pretreated with 17beta-estradiol (200 microg/rat, subcutaneously). Furthermore, increased gastroduodenal mucus levels were found in early-stage pregnancy rats and in animals pretreated with progesterone. These results suggest that increased progesterone plasma levels during early-stage pregnancy may be involved in pregnancy-induced gastric and duodenal protection. This effect may be related to an increase in gastric and duodenal mucus production induced by this hormone.

  7. Role of sodium depletion in acute antidiuretic effect of bendroflumethiazide in rats with nephrogenic diabetes insipidus.

    Science.gov (United States)

    Janjua, N R; Jonassen, T E; Langhoff, S; Thomsen, K; Christensen, S

    2001-10-01

    The mechanisms underlying the acute antidiuretic response to bendroflumethiazide (BFTZ; 0.25 mg/h for 3 h) in rats with nephrogenic diabetes insipidus (NDI) was investigated. NDI was induced in conscious chronically instrumented female Wistar rats either by chronic lithium administration (40-60 mmol Li/kg of diet for 4 weeks) or by acute infusion of V2 antagonist OPC-31260 (0.2 mg/h). Renal clearance experiments were performed in conscious rats instrumented with permanent catheters. During experiments total body water content was held constant by i.v. replacement of urine production (V) with 150 mM glucose. One group in addition received i.v. replacement of urinary sodium losses. In both models of NDI, BFTZ-induced antidiuresis was associated with a decrease in the delivery of tubular fluid to the distal nephron, as measured by lithium clearance (C(Li)). Both the antidiuresis and the decrease in C(Li) could be prevented by sodium replacement. BFTZ did not affect distal water handling as measured by V/C(Li). BFTZ did not induce antidiuresis in normal rats with water diuresis. It is concluded that in rats with NDI, thiazide-induced antidiuresis can be entirely explained by a fall in distal delivery of tubular fluid related to sodium depletion. This contrasts the response in rats with central diabetes insipidus, where thiazides in addition increase distal water reabsorption.

  8. High Autophagy in the Naked Mole Rat may Play a Significant Role in Maintaining Good Health

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-02-01

    Full Text Available Background/Aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice. Methods: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry. Results: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old and adult C57BL/6 mice (eight weeks old have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases. Conclusion: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

  9. [The role of arecoline on hepatic insulin resistance in type 2 diabetes rats].

    Science.gov (United States)

    Ling, Hong-Yan; Yao, Qi-Xin; Qi, Zhu-Qing; Yang, Si-Si; He, Jian-Qin; Zhang, Kai-Fang; Hu, Bi

    2014-05-01

    To explore the effects of arecoline on hepatic insulin resistance in type 2 diabetes rats and to elucidate its possible mechanism. Forty five Wistar rats were fed with high fructose diet for 12 weeks to induce type 2 diabetic rat model. rats were randomly divided into 5 groups (n = 8): control group, model group and model group were treated with different dose (0, 0.5, 1, 5 mg/kg) of arecoline. After 4 weeks, the fasting blood glucose, blood lipid and insulin level measured , mRNA expression of liver constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by reverse transcription polymerase chain reaction (RT-PCR), the protein expression of p-AKT and glucose transporter4 (GLUT4) were detected by Western blot. 1.5 mg/kg arecoline could significantly decrease the level of fasting blood glucose, blood lipid, blood insulin level and liver G6Pase, PEPCK, IL-6, TNF-alpha mRNA level in type 2 diabetes rats. 1.5 mg/kg arecoline also could significantly increase CAR, PXR mRNA level and p-AKT and GLUT4 protein expression. Arecoline improved hepatic insulin resistance in type 2 diabetes rats by increasing the mRNA levels of CAR and PXR leading to the creased glucose metabolism and inflammation related genes expression.

  10. Sex differences in social interaction in rats: role of the immediate-early gene zif268.

    Science.gov (United States)

    Stack, Ashley; Carrier, Nicole; Dietz, David; Hollis, Fiona; Sorenson, Jamie; Kabbaj, Mohamed

    2010-01-01

    Given both the high prevalence of anxiety disorders in women and the fact that little is known about the mechanisms of gender differences in anxiety, our primary aim in this study was to investigate the neurobiological mechanisms underlying sex differences in social anxiety-like behavior in rats. Through the use of zif268 antisense oligodeoxynucleotides (zif ASO), we induced a temporary downregulation of zif268 expression in the medial prefrontal cortex of male and female rats and found that zif268 ASO male rats show more social anxiety-like behaviors when compared with control male rats in the social interaction test. In fact, zif268 ASO males displayed social anxiety-like behaviors, which were similar to control females, thus downregulation of zif268 expression in the mPFC of male rats eliminated sex differences previously found in the social anxiety-like behavior tests. Interestingly, zif268 ASO in female rats had no effect on their social interaction. Our novel findings have led us to ascertain that sexually dimorphic zif268 expression in the mPFC is a key molecular factor in mediating sex-specific anxiety-like behavior in the social interaction test.

  11. Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats.

    Science.gov (United States)

    Nakata, T; Takeda, K; Harada, S; Oguni, A; Hatta, T; Kawa, T; Itoh, H; Sasaki, S; Nakagawa, M

    2001-01-01

    We examined the role of the central nervous system, and particularly the renin-angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank either nitro-L-arginine-methyl ester (L-NAME) or tap water. Before L-NAME treatment rats were divided into 6 groups. Four of them were administered either losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventricularly (i.c.v.) for 1 week using an osmotic mini pump. The other two groups were administered the same amount of losartan intravenously (i.v.). In experiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol, a GABA(A) agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AV3V (anteroventral third ventricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hypertension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v. losartan, blood pressure was elevated to the same level as in a-CSF-infused, L-NAME-treated rats. Acute i.c.v. losartan produced no cardiovascular changes in either L-NAME-treated or control rats. On the other hand, although i.c.v. muscimol elicited depressor effects in both groups, these responses were significantly larger in L-NAME-treated rats. Cardiovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the development of L-NAME-induced hypertension. These results indicate that the central RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase. Moreover, disorder of the central GABA system, rather than that of the RA system, might be important in the maintenance of hypertension in this model.

  12. Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

    Directory of Open Access Journals (Sweden)

    Hsin-Ju Tsai

    Full Text Available Our previous studies demonstrated that remote electro-stimulation (RES increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R injury in rat hearts. However, the role of various opioid receptors (OR subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR subtype receptors (KOR, DOR, and MOR. The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left, RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left were 50%, 20%, 67%, 13%, 50% and 55%, respectively.The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.

  13. Varieties of conventional implicature

    Directory of Open Access Journals (Sweden)

    Eric Scott McCready

    2010-07-01

    Full Text Available This paper provides a system capable of analyzing the combinatorics of a wide range of conventionally implicated and expressive constructions in natural language via an extension of Potts's (2005 L_CI logic for supplementary conventional implicatures. In particular, the system is capable of analyzing objects of mixed conventionally implicated/expressive and at-issue type, and objects with conventionally implicated or expressive meanings which provide the main content of their utterances. The logic is applied to a range of constructions and lexical items in several languages. doi:10.3765/sp.3.8 BibTeX info

  14. A regulatory role of androgen in ovarian steroidogenesis by rat granulosa cells.

    Science.gov (United States)

    Hasegawa, Toru; Kamada, Yasuhiko; Hosoya, Takeshi; Fujita, Shiho; Nishiyama, Yuki; Iwata, Nahoko; Hiramatsu, Yuji; Otsuka, Fumio

    2017-09-01

    Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of androgen on steroidogenesis, DHT enhanced the expression of progesterogenic factors and enzymes, including StAR, P450scc and 3βHSD, and cellular cAMP synthesis induced by FSH and IGF-I. Of note, treatment with DHT and IGF-I suppressed Smad1/5/8 phosphorylation and transcription of the BMP target gene Id-1, suggesting that androgen and IGF-I counteract BMP signaling that inhibits FSH-induced progesterone synthesis in rat granulosa cells. DHT was revealed to suppress the expression of BMP-6 receptors, consisting of ALK-2, ALK-6 and ActRII, while it increased the expression of inhibitory Smads in rat granulosa cells. In addition, IGF-I treatment upregulated androgen receptor (AR) expression and DHT treatment suppressed IGF-I receptor expression on rat granulosa cells. Collectively, the results indicate that androgen and IGF-I mutually interact and accelerate progesterone production, at least in part, by regulating endogenous BMP signaling in rat granulosa cells. Cooperative effects of androgen and IGF-I counteract endogenous BMP-6 activity in rat granulosa cells, which is likely to be functionally linked to the steroidogenic property shown in the PCOS ovary. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Antigen-induced pleural eosinophilia is suppressed in diabetic rats: role of corticosteroid hormones

    Directory of Open Access Journals (Sweden)

    Bruno L Diaz

    1997-12-01

    Full Text Available Previous studies have evidenced for the existence of interactive regulatory mechanisms between insulin and steroid hormones in different systems. In this study, we have investigated whether endogenous corticosteroids could be implicated in the hyporeactivity to antigen challenge observed in sensitized diabetic rats. Alloxinated rats showed a long-lasting increase in the blood glucose levels and a reduction in the number of pleural mast cells at 48 and 72 hr, but not at 24 hr after alloxan administration. In parallel, they also showed a significant elevation in the plasma levels of corticosterone together with an increase in the adrenal/body weight ratio. Antigen-evoked eosinophil accumulation appeared significantly reduced in rats pretreated with dexamethasone as well as in those rendered diabetic 72 hr after alloxan. In the same way, naive animals treated with dexamethasone also responded with a significant decrease in the number of pleural mast cells. Interestingly, when sensitized diabetic rats were pretreated with the steroid antagonist RU 38486 a reversion of the reduction in the allergen-induced eosinophil accumulation was noted. We conclude that the down-regulation of the allergic inflammatory response in diabetic rats is close-related to reduction in mast cell numbers and over expression of endogenous corticosteroids.

  16. Modulatory role of kolaviron in phenytoin-induced hepatic and testicular dysfunctions in Wistar rats.

    Science.gov (United States)

    Owoeye, Olatunde; Adedara, Isaac A; Adeyemo, Oluwatobi A; Bakare, Oluwafemi S; Egun, Christa; Farombi, Ebenezer O

    2015-03-01

    Phenytoin, an anticonvulsant agent used for the treatment of epilepsy has been reported to exhibit toxic side effects on the liver and testes. The present study investigated the protective effects of kolaviron (KV, a bioflavonoid from Garcinia kola seeds) against hepatic and testicular damage in rats exposed to phenytoin. The study consisted of four groups of six rats per group. Group I rats received 2 mL/kg of corn alone while group II received 75 mg/kg of phenytoin (PHT) alone. Groups III and IV were co-treated with kolaviron (200 mg/kg KV) and vitamin E (500 mg/kg VTE), respectively, for 14 days. The antioxidant status, hepatic and reproductive functional parameters were subsequently determined. PHT treatment significantly (p testicular levels of glutathione (GSH). Moreover, PHT exposure elicited significant increases in alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels. The significant reduction in seminal epithelium thickness and the diameter of seminiferous tubules was accompanied with marked decrease in sperm motility, sperm count, and viability in PHT-treated rats. However, antioxidant status and the functional indices of liver and testes were restored to near control levels in rats co-treated with KV and VTE. In conclusion, KV and VTE protect the liver and testes against functional impairment due to PHT treatment.

  17. THE ROLE OF VENTRAL MIDLINE THALAMUS IN CHOLINERGIC-BASED RECOVERY IN THE AMNESTIC RAT

    Science.gov (United States)

    Bobal, Michael G.; Savage, Lisa M.

    2014-01-01

    The thalamus is a critical node for several pathways involved in learning and memory. Damage to the thalamus by trauma, disease or malnourishment can impact the effectiveness of the prefrontal cortex (PFC) and hippocampus (HPC) and lead to a profound amnesia state. Using the pyrithiamine-induced thiamine deficiency (PTD) rat model of human Wernicke-Korsakoff syndrome, we tested the hypothesis that co-infusion of the acetylcholinesterase inhibitor physostigmine across the PFC and HPC would recover spatial alternation performance in PTD rats. When cholinergic tone was increased by dual injections across the PFC-HPC, spontaneous alternation performance in PTD rats was recovered. In addition, we tested a second hypothesis that two ventral midline thalamic nuclei, the rhomboid nucleus and nucleus reuniens (Rh-Re), form a critical node needed for the recovery of function observed when cholinergic tone was increased across the PFC and HPC. By using the GABAA agonist muscimol to temporarily deactivate the Rh-Re the recovery of alternation behavior obtained in the PTD model by cholinergic stimulation across the PFC-HPC was blocked. In control pair-fed (PF) rats, inactivation of the Rh-Re impaired spontaneous alternation. However, when inactivation of the Rh-Re co-occurred with physostigmine infusions across the PFC-HPC, PF rats had normal performance. These results further demonstrate that the Rh-Re is critical in facilitating interactions between the HPC and PFC, but other redundant pathways also exist. PMID:25446352

  18. Role of CCL3/MIP-1alpha and CCL5/RANTES during acute Trypanosoma cruzi infection in rats.

    Science.gov (United States)

    Roffê, Ester; Oliveira, Fabiano; Souza, Adriano L S; Pinho, Vanessa; Souza, Danielle G; Souza, Patrícia R S; Russo, Remo C; Santiago, Helton C; Romanha, Alvaro J; Tanowitz, Herbert B; Valenzuela, Jesus G; Teixeira, Mauro M

    2010-08-01

    Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-gamma production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.

  19. Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome.

    Science.gov (United States)

    Zou, Bai-cang; Dong, Lei; Wang, Yan; Wang, Sheng-hao; Cao, Ming-bo

    2007-12-05

    The 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS. A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT(7) receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.

  20. Age and heat exposure-dependent changes in antioxidant enzymes activities in rat's liver and brain mitochondria: role of alpha-tocopherol.

    Science.gov (United States)

    Stojkovski, V; Hadzi-Petrushev, N; Ilieski, V; Sopi, R; Gjorgoski, I; Mitrov, D; Jankulovski, N; Mladenov, M

    2013-01-01

    To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.

  1. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

    DEFF Research Database (Denmark)

    Schmal, H; Shanley, T P; Jones, M L;

    1996-01-01

    Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab...... to the 7.9-kDa peptide showed reactivity by western blot analysis and suppressed its in vitro chemotactic activity. Cross-desensitization chemotaxis experiments suggested that the chemotactic responses elicited by MIP-2 and the related chemokine, cytokine-induced neutrophil chemoattractant, may be mediated...... through a common receptor. Also, chemotactic responses to human GRO-alpha were blocked by exposure of human neutrophils to either GRO-alpha or rat MIP-2, suggesting conservation of this receptor-mediated response. After LPS instillation into rat lung, mRNA for MIP-2 was up-regulated in a time...

  2. Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

    Science.gov (United States)

    Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

    1998-01-01

    We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

  3. Brain edema after intracerebral hemorrhage in rats: The role of inflammation

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    Zhang Xiangjian

    2006-01-01

    Full Text Available Background: Intracerebral hemorrhage (ICH results in secondary brain edema and injury that may lead to death and disability. ICH also causes inflammation. It is unclear whether inflammation contributes to brain edema and neuron injury or functions in repairing the brain tissue. Aims: To understand the effect of inflammation in ICH, we have carried out an investigation on the various aspects and the dynamic changes of inflammation. Settings and Design: An ICH model was generated by injecting 50 ml autologous tail artery blood stereotactically into the right caudate nucleus of 30 rats, which were randomly divided into five ICH groups. Similarly, five Sham control groups were generated by inserting the needle to the right caudate nucleus of rats. Materials and Methods: Rat behavior was evaluated over the time course (6 h, 24 h, 48 h, 72 h and 7 d in each group. The rats were then killed by administering an overdose of pentobarbital. Following the euthanasia, the brain water content, neuronal loss, glia proliferation, inflammatory infiltration and brain morphology of the rats were measured. Additionally, the expression of TNF-a,IL-6, ICAM-1, VEGF, NF-kB, C3 and CR2 was analyzed by immunohistochemistry. Statistical Analysis: The data were analyzed by student′s t test. Results: Rat brain water content increased progressively over the time course and reached its peak at 48h followed ICH. The maximum of inflammatory infiltrate (especially neutrophils and immunopositive cells of TNF-a, IL-6 and NF-kB, were at 48h. The expression of C3 and CR2 reached their peaks at 48-72h, while the expression ICAM-1 and VEGF were at maximum at 72h followed ICH. Conclusions: The results suggested that the inflammatory cytokines, complement system and VEGF may have a function in the development of the brain edema and neuron injury followed ICH.

  4. Protective role of Cynodon dactylon in ameliorating the aluminium-induced neurotoxicity in rat brain regions.

    Science.gov (United States)

    Sumathi, Thangarajan; Shobana, Chandrasekar; Kumari, Balasubramanian Rathina; Nandhini, Devarajulu Nisha

    2011-12-01

    Cynodon dactylon (Poaceae) is a creeping grass used as a traditional ayurvedic medicine in India. Aluminium-induced neurotoxicity is well known and different salts of aluminium have been reported to accelerate damage to biomolecules like lipids, proteins and nucleic acids. The objective of the present study was to investigate whether the aqueous extract of C. dactylon (AECD) could potentially prevent aluminium-induced neurotoxicity in the cerebral cortex, hippocampus and cerebellum of the rat brain. Male albino rats were administered with AlCl(3) at a dose of 4.2 mg/kg/day i.p. for 4 weeks. Experimental rats were given C. dactylon extract in two different doses of 300 mg and 750 mg/keg/day orally 1 h prior to the AlCl(3) administration for 4 weeks. At the end of the experiments, antioxidant status and activities of ATPases in cerebral cortex, hippocampus and cerebellum of rat brain were measured. Aluminium administration significantly decreased the level of GSH and the activities of SOD, GPx, GST, Na(+)/K(+) ATPase, and Mg(2+) ATPase and increased the level of lipid peroxidation (LPO) in all the brain regions when compared with control rats. Pre-treatment with AECD at a dose of 750 mg/kg b.w increased the antioxidant status and activities of membrane-bound enzymes (Na(+)/K(+) ATPase and Mg(2+) ATPase) and also decreased the level of LPO significantly, when compared with aluminium-induced rats. The results of this study indicated that AECD has potential to protect the various brain regions from aluminium-induced neurotoxicity.

  5. Possible role for TRPV1 in neomycin-induced inhibition of visceral hypersensitivity in rat.

    Science.gov (United States)

    van den Wijngaard, R M; Welting, O; Bulmer, D C; Wouters, M M; Lee, K; de Jonge, W J; Boeckxstaens, G E

    2009-08-01

    Transient receptor ion channel 1 (TRPV1) is a nociceptor involved in visceral hypersensitivity. Aminoglycosides like neomycin are not only potent antibiotics but in vitro data suggest that neomycin also acts as a TRPV1-antagonist and alleviates somatic pain responses. To what extent neomycin reduces visceral hypersensitivity remains unknown. Therefore, we aimed to investigate whether neomycin can inhibit in vivo TRPV1-dependent hypersensitivity responses in two rat models of visceral pain. In the first model rats were pretreated with intraperitoneal (i.p.) capsazepine, the selective TRPV1 antagonist SB-705498, neomycin or vehicle alone and 30 min later instilled with intracolonic TRPV1-activating capsaicin. Likewise, rats were pretreated with 10 days oral neomycin and then subjected to intracolonic capsaicin. The visceromotor response (VMR) to distension was measured before and after capsaicin application. In addition, the VMR to distension was measured in adult maternal separated rats before and after acute stress. Before the 2nd distension protocol these rats were treated with i.p. neomycin, amoxycillin or vehicle alone. Our results showed that capsaicin administration induced an enhanced VMR to distension that was prevented by i.p. capsazepine, SB-705498 and neomycin. Oral neomycin treatment changed bacterial faecal content but could not inhibit capsaicin induced visceral hypersensitivity. In maternal separated rats acute stress induced an enhanced response to distension that was reversed by i.p. neomycin, but not amoxycillin. These data indicate that (i.p.) neomycin can inhibit visceral hypersensitivity to distension in a nonbactericidal manner and suggest that TRPV1-modulation may be involved.

  6. Role of exercise training in cardiovascular autonomic dysfunction and mortality in diabetic ovariectomized rats.

    Science.gov (United States)

    Souza, Silvia B C; Flues, Karin; Paulini, Janaina; Mostarda, Cristiano; Rodrigues, Bruno; Souza, Leandro E; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2007-10-01

    Diabetes and menopause markedly increase the risk of cardiovascular disease in women. The objective of the present study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction and on total mortality in diabetic female rats undergoing ovarian hormone deprivation. Female Wistar rats were divided into ovariectomized groups: sedentary and trained controls and sedentary and trained diabetic rats (streptozotocin, 50 mg/kg IV). Trained groups were submitted to an exercise training protocol on a treadmill (8 weeks). The baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes. Heart rate variability was determined using the SD of the basal heart rate. Vagal and sympathetic tonus were evaluated by pharmacological blockade. Diabetes impaired baroreflex sensitivity ( approximately 55%), vagal tonus ( approximately 68%), and heart rate variability ( approximately 38%). Exercise training improved baroreflex sensitivity and heart rate variability in control and diabetic groups in relation to their sedentary groups. Trained control rats presented increased vagal tonus compared with that of sedentary ones. The sympathetic tonus was reduced in the trained diabetic group as compared with that of other studied groups. Significant correlations were obtained between heart rate variability and vagal tonus with baroreflex sensitivity. Mortality, assessed during the training period, was reduced in trained diabetic (25%) rats compared with mortality in sedentary diabetic rats (60%). Together, these findings suggest that decreases in baroreflex sensitivity and heart rate variability may be related to increased mortality in female diabetic subjects and that improved autonomic regulation induced by exercise training may contribute to decreased mortality in this population.

  7. The role of carnitine on ovariectomy and inflammation-induced osteoporosis in rats.

    Science.gov (United States)

    Orsal, Ebru; Halici, Zekai; Bayir, Yasin; Cadirci, Elif; Bilen, Habib; Ferah, Irmak; Aydin, Ali; Ozkanlar, Seckin; Ayan, Arif Kursad; Seven, Bedri; Ozaltin, Seda

    2013-12-01

    This study was carried out to assess the protective bone-sparing effect of carnitine with anti-inflammatory properties on chronic inflammation-induced bone loss in ovariectomised (OVX) rats. A total of 64 rats were divided into eight groups. Sixteen rats were sham-operated (SH) while the others were ovariectomised (OVX). (1) SH, (2) sham + inflammation (SHinf), (3) OVX, (4) ovariectomy + inflammation (OVXinf), (5) OVX + CAR1, (6) OVX + CAR2, (7) OVXinf + CAR1, (8) OVXinf + CAR2. After the ovariectomy surgery, all the groups (3, 4, 5, 6, 7, and 8) were allowed to recover for two months. Sixty days after the OVX, inflammation was induced by subcutaneous injections of talc in groups 2, 4, 7, and 8. Group 5 and 7 were given 50 mg/kg CAR; Group 6 and 8 were given 100 mg/kg CAR from the 60th to the 80th day. Serum levels of TNF-α, IL-1, IL-6, OP, and OC were assessed to determine inflammation and to evaluate osteoblastic activity. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry in femur bones of rats. Carnitine administration was able to restore BMD up to values measured in both the OVX and the SH animals. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. In OVX rats, inflammation which is evaluated by serum cytokine levels exacerbated this bone loss, as supported by values of BMD of the total femur. The two different doses of carnitine reduced bone loss and improved inflammatory biomarkers.

  8. Protective role of caffeic acid on lambda cyhalothrin-induced changes in sperm characteristics and testicular oxidative damage in rats.

    Science.gov (United States)

    Abdallah, Fatma Ben; Fetoui, Hamadi; Zribi, Nassira; Fakhfakh, Feiza; Keskes, Leila

    2012-08-01

    The synthetic pyrethroids are expected to cause deleterious effects on most of the organs and especially on the male reproductive system. The current study was performed to assess the adverse effect of lambda cyhalothrin (LC) on reproductive organs and fertility in male rats and to evaluate the protective role of caffeic acid phenethyl ester (CAPE) in alleviating the detrimental effect of LC on male fertility. A total of 48 male rats were divided into 4 groups (12 rats each): control group received distilled water ad libitum and 1 ml of vehicle solution given intraperitoneally (i.p.); CAPE-treated group received a single i.p. dose of CAPE (10 μmol kg⁻¹ day⁻¹); LC-treated group received 668 ppm of LC through drinking water; and CAPE + LC-treated group received an i.p. injection of CAPE (10 μmol kg⁻¹ day⁻¹) 12 h before the LC administration. The experiment was conducted for 10 consecutive weeks. LC caused a significant increase in testicular malondialdehyde, catalase, superoxide dismutase, glutathione-S-transferase activities, and sperm abnormalities and a significant reduction in testicular glutathione concentration, sperm count, sperm motility, and a live sperm percentage. Conversely, treatment with CAPE improved the reduction in the sperm characteristics, LC-induced oxidative damage of testes and the testicular histopathological alterations. Results indicate that LC exerts significant harmful effects on the male reproductive system and that CAPE reduced the deleterious effects of LC on male fertility.

  9. Uterine autonomic nerve innervation plays a crucial role in regulating rat uterine mast cell functions during embryo implantation.

    Science.gov (United States)

    Yuan, Xue-Jun; Huang, Li-Bo; Qiao, Hui-Li; Deng, Ze-Pei; Fa, Jing-Jing

    2009-12-01

    To explore the potential mechanism of how uterine innervations would affect the uterine mast cell (MC) population and functions during the periimplantation. We herein first examined the consequence of uterine neurectomy on embryo implantation events. We observed that amputation of autonomic nerves innervating the uterus led to on-time implantation failure in rats. Exploiting MC culture and ELISA approaches, we then further analyzed the effect of neurectomy on cellular histamine levels and its release from uterine MCs, to elucidate the relation of the autonomic nerves and local cellular immunity in the uterine during early pregnancy. We observed that disconnection of autonomic nerve innervation significantly increased the population of uterine MCs. Most interestingly, these increased number of uterine MCs in neuroectomized rats contained a much reduced cellular level of histamine. Our subsequent challenge experiments revealed that uterine MCs in nerve amputated rats exhibited enhanced histamine releasing rate in response to substance P and antiIgE, suggesting loss of nerve innervation in the uterus not only increases the population of uterine MCs, but also facilitates the release of histamine from MCs, thus subsequently interfere with the normal implantation process. Collectively, our findings provide a new line of evidence supporting the concept that immune-neuro-endocrine network plays important role during pregnancy establishment and maintenance.

  10. The potential role of Azadirachta indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in female rats.

    Science.gov (United States)

    Dkhil, Mohamed A; Al-Quraishy, Saleh; Aref, Ahmed M; Othman, Mohamed S; El-Deib, Kamal M; Abdel Moneim, Ahmed E

    2013-01-01

    Azadirachta indica A. Juss. (neem, family: Meliaceae) is perhaps the most commonly used traditional medicinal plant of India. In this study we investigated the protective effect of methanolic neem leaves extract (MNLE; 500 mg/Kg bwt) on rats treated with cisplatin (CDDP)-induced hepatotoxicity. Adult rats were randomly divided into four groups. CDDP was given to rats by intraperitoneal injection, while MNLE was given by oral gavage for 5 days after the CDDP injection. The injury and oxidative stress caused by CDDP on the liver and the effect of MNLE were evaluated by measuring (a) histological changes, (b) tissue biochemical oxidant and antioxidant parameters, and (c) investigating apoptosis markers immunohistochemically and by real time PCR. After treatment with MNLE, the histological damage and apoptosis induction caused by cisplatin were improved. Malondialdehyde and nitric oxide were significantly decreased; the antioxidant system, namely, glutathione content, glutathione-S-transferase, glutathione peroxidase, catalase, and superoxide dismutase activities were significantly elevated. In conclusion, MNLE may have a potential role when combined with cisplatin in chemotherapy to alleviate cisplatin-induced damage and oxidative stress in liver.

  11. The Potential Role of Azadirachta indica Treatment on Cisplatin-Induced Hepatotoxicity and Oxidative Stress in Female Rats

    Directory of Open Access Journals (Sweden)

    Mohamed A. Dkhil

    2013-01-01

    Full Text Available Azadirachta indica A. Juss. (neem, family: Meliaceae is perhaps the most commonly used traditional medicinal plant of India. In this study we investigated the protective effect of methanolic neem leaves extract (MNLE; 500 mg/Kg bwt on rats treated with cisplatin (CDDP-induced hepatotoxicity. Adult rats were randomly divided into four groups. CDDP was given to rats by intraperitoneal injection, while MNLE was given by oral gavage for 5 days after the CDDP injection. The injury and oxidative stress caused by CDDP on the liver and the effect of MNLE were evaluated by measuring (a histological changes, (b tissue biochemical oxidant and antioxidant parameters, and (c investigating apoptosis markers immunohistochemically and by real time PCR. After treatment with MNLE, the histological damage and apoptosis induction caused by cisplatin were improved. Malondialdehyde and nitric oxide were significantly decreased; the antioxidant system, namely, glutathione content, glutathione-S-transferase, glutathione peroxidase, catalase, and superoxide dismutase activities were significantly elevated. In conclusion, MNLE may have a potential role when combined with cisplatin in chemotherapy to alleviate cisplatin-induced damage and oxidative stress in liver.

  12. Role of the sympatho-adrenal system in the reflex tachycardia produced by hydralazine in the anesthetized rat.

    Science.gov (United States)

    Vidrio, H; García-Márquez, F

    1986-09-01

    The role of the sympatho-adrenal system in the production of tachycardia accompanying the hypotensive response to hydralazine was studied in urethane-anesthetized rats subjected to previous bilateral adrenal demedullation or to pretreatment with 6-hydroxydopamine and compared with intact control animals. The prolonged hypotension induced by the vasodilator was not affected by these maneuvers, but the slowly developing tachycardia was reversed to bradycardia, which in the demedullated group was followed after 60 min by a moderate increase in heart rate. In the chemically sympathectomized rats, the cardiac depressant response was completely blocked by pretreatment with atropine. In additional experiments, previous administration of methylatropine enhanced hydralazine tachycardia, but atropine partially inhibited this response and changed its time course to mirror that of the hypotension. These results indicate that in urethane-anesthetized rats, hydralazine tachycardia is mediated by sympatho-adrenal activation and that it is accompanied by a simultaneous heart rate-lowering parasympathetic discharge normally masked by the predominant tachycardia. They further suggest that the tachycardia is facilitated by a muscarinic mechanism which modulates central sympathetic influences on cardiovascular function.

  13. Role of the gap junctions in the contractile response to agonists in pulmonary artery from two rat models of pulmonary hypertension

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    Dahan Diana

    2011-03-01

    Full Text Available Background Pulmonary hypertension (PH is characterized by arterial vascular remodelling and alteration in vascular reactivity. Since gap junctions are formed with proteins named connexins (Cx and contribute to vasoreactivity, we investigated both expression and role of Cx in the pulmonary arterial vasoreactivity in two rat models of PH. Methods Intrapulmonary arteries (IPA were isolated from normoxic rats (N, rats exposed to chronic hypoxia (CH or treated with monocrotaline (MCT. RT-PCR, Western Blot and immunofluorescent labelling were used to study the Cx expression. The role of Cx in arterial reactivity was assessed by using isometric contraction and specific gap junction blockers. Contractile responses were induced by agonists already known to be involved in PH, namely serotonin, endothelin-1 and phenylephrine. Results Cx 37, 40 and 43 were expressed in all rat models and Cx43 was increased in CH rats. In IPA from N rats only, the contraction to serotonin was decreased after treatment with 37-43Gap27, a specific Cx-mimetic peptide blocker of Cx 37 and 43. The contraction to endothelin-1 was unchanged after incubation with 40Gap27 (a specific blocker of Cx 40 or 37-43Gap27 in N, CH and MCT rats. In contrast, the contraction to phenylephrine was decreased by 40Gap27 or 37-43Gap27 in CH and MCT rats. Moreover, the contractile sensitivity to high potassium solutions was increased in CH rats and this hypersensitivity was reversed following 37-43Gap27 incubation. Conclusion Altogether, Cx 37, 40 and 43 are differently expressed and involved in the vasoreactivity to various stimuli in IPA from different rat models. These data may help to understand alterations of pulmonary arterial reactivity observed in PH and to improve the development of innovative therapies according to PH aetiology.

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

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    Firas eSedki

    2013-06-01

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

  15. Role of epinephrine for muscular glycogenolysis and pancreatic hormonal secretion in running rats

    DEFF Research Database (Denmark)

    Richter, Erik; Sonne, B; Christensen, N J;

    1981-01-01

    We have previously shown that during swimming muscular glycogen breakdown was diminished and plasma glucagon and insulin were lower and higher, respectively, in adrenodemedullated rats compared to controls. These findings might be due to a lower work intensity or higher efficiency in adrenodemedu......We have previously shown that during swimming muscular glycogen breakdown was diminished and plasma glucagon and insulin were lower and higher, respectively, in adrenodemedullated rats compared to controls. These findings might be due to a lower work intensity or higher efficiency...

  16. Role of candesartan against cerebral ischemia and oxidative damage in normotensive rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective Angiotensin Ⅱ(Ang Ⅱ)contributes to modulating blood pressure by stimulation of Ang Ⅱ AT1 receptors.We devised a rat transient middle cerebral artery occlusion(MCAO)model to assess whether oxidative damage is decreased after pretreatment with Angiotensin Ⅱ AT1 receptor blocker(ARB).Methods After 2 weeks pretreatment with ARB 0.5 and 1mg/kg,the male Wister rats were subjected to 2h middle cerebral artery occlusion(MCAO).At 24h,the lumen diameter of middle cerebral artery,the plasma level of 8-hydrox...

  17. Triggering role of nitric oxide in the delayed protective effect of monophosphoryl lipid A in rat heart

    Science.gov (United States)

    György, Katalin; Muller, Bernard; Végh, Agnes; Kleschyov, Andrei L; Stoclet, Jean-Claud

    1999-01-01

    The main objective of the present study was to further evaluate the role of nitric oxide (NO) in delayed cardiac protection against ischaemia-reperfusion injury induced by monophosphoryl lipid A (MLA).For this purpose, rats were administered with either 0.5 or 2.5 mg kg−1 MLA (i.p.). Eight or 24 h later, in vivo NO production in the heart was analysed by electron paramagnetic resonance (EPR) spin trapping technique. In parallel experiments, hearts were removed and perfused according to Langendorff. Functional ventricular parameters and incidence of ventricular fibrillation (VF) were determined after 30 min global ischaemic insult (37°C) followed by 30 min reperfusion. Vascular reactivity of aortic rings was also assessed.Hearts from rats pretreated with 2.5 mg kg−1 MLA for 24 h (but not those from rats treated with 0.5 mg kg−1 MLA for 8 and 24 h, or with 2.5 mg kg−1 MLA for 8 h) exhibited preservation of ventricular function (LVDP, ±dP/dtmax) and a reduced incidence of VF (25% vs 87.5% in vehicle control) during reperfusion. At the cardioprotective dose of 2.5 mg kg−1 (for 8 or 24 h), MLA did not produce alterations of the contractile response of aortic rings to noradrenaline.An increased formation of NO was detected in hearts removed from rats pretreated with 2.5 mg kg−1 MLA for 8 h, but not in those from rats treated for 24 h (or with 0.5 mg kg−1 MLA).Pretreatment of the animals with the inhibitors of inducible NO-synthase, aminoguanidine (2×300 mg kg−1) or L-N6-(1-Iminoethyl)-lysine (L-NIL, 10 mg kg−1) abolished both MLA (2.5 mg kg−1)-induced rise of NO production (observed 8 h after MLA) and cardioprotection (observed 24 h after MLA). However MLA-induced cardioprotection was not attenuated when the hearts were perfused with aminoguanidine (150 μM) for 30 min before the ischaemic insult.Altogether, the present data suggest that NO acts as a trigger rather then a direct

  18. Cardiac protective role of a novel erythrocyte-derived depressing factor on rats and its Ca2+ mechanism

    Institute of Scientific and Technical Information of China (English)

    WANG Yutang; WEN Yunyi; MA Ning; SHI Lei

    2003-01-01

    The cardiac protective role of a novel erythrocyte-derived depressing factor (EDDF) on spontaneous hypertensive rats (SHR), calcium overload (CaO) rats and Wistar rats and its mechanism was evaluated. Mean artery pressure (MAP), heart rate (HR) and LVdp/dtmax were measured by physiological recorder. The effect of EDDF on the Ca2+-ATPase activity in myocardial sarcoplasmic reticulum (SR) of CaO rats was determined by inorganic phosphate assay. Calcium transport in myocytes was measured by 45Ca2+ radioactive isotope measurement. The phosphorylation levels of extracellular signal-regulated protein kinases (ERK1/2) in myocardial tissue of SHR and CaO rats were measured by Western blot method. And the ultrastructures of cardiac muscle cells were observed with the transmission electron microscope. The results indicated that EDDF could significantly decrease MAP, HR and LVdp/dtmax in a dose dependent manner (P < 0.05). It seems that the mechanism might relate with activating the Ca2+-APTase, enhancing the uptake and release of Ca2+ from SR (P < 0.05), decreasing the phosphorylation levels of ERK1/2 of myocytes (P < 0.01) and lightening the ultrastructural lesion of cardiac muscle cells. In CaO rats, the Ca2+-ATPase activity decreased clearly compared to control (64.99 ± 7.16 vs 94.48 ± 7.68 nmol·min-1·mg-1 protein, P < 0.01), while EDDF (100 μg/mL) could significantly increase the activity (87.93 ± 9.54 vs 64.99 ± 7.16, P < 0.05, n = 7). Both uptake and release rate of Ca2+ (μmol 45Ca2+/g protein/min) from myocardial SR of CaO rats remarkably decreased compared to control (32.40 ± 2.70 and 15.46 ± 1.49 vs 61.09 ± 10.89 and 25.47 ± 4.29, P < 0.05); EDDF (100 μg/mL) could significantly stimulate their activities (50.48 ± 6.76 and 21.76 ± 2.75 vs 32.40 ± 2.70 and 15.46 ± 1.49, P < 0.05). EDDF could evidently down-regulate the phosphorylation of ERK1/2 in myocardial tissue from SHR and CaO rats (P < 0.01), lighten the ultrastructural lesion of cardiac muscle

  19. Fermentation enhances Ginkgo biloba protective role on gamma-irradiation induced neuroinflammatory gene expression and stress hormones in rat brain.

    Science.gov (United States)

    Ismail, Amel F M; El-Sonbaty, Sawsan M

    2016-05-01

    Ionizing radiation has attracted a lot of attention due to its beneficial and possible harmful effects to the human population. The brain displays numerous biochemical and functional alterations after exposure to irradiation, which induces oxidative-stress through generation of reactive oxygen species (ROS). The present study evaluated the neuro-protective role of fermented Ginkgo biloba (FGb) leaf extract, compared to non-fermented G. biloba (Gb) leaf extract against γ-irradiation (6Gy) in the rats' brain. The changes of the Gb phytochemical constituents after fermentation, using Aspergillus niger were evaluated by Gas Chromatography-Mass Spectrometry. The results showed a significant decrease in superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and elevation of the calcium level in the brain cytosolic fraction of γ-irradiated rats. Further, significant increases in the malondialdehyde (MDA), the stress hormones (catecholamines); epinephrine (EN), norepinephrine (NE) and dopamine (DA) levels and the interleukin-1-beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) gene expression relative ratio in parallel with a significant decrease in the glutathione (GSH) content and DNA fragmentation in the brain tissues of the γ-irradiated rats were observed. The pre-treatment with Gb extract significantly amended these biochemical parameters. Meanwhile, the pre-treatment with the FGb showed more improvement, compared to Gb, of these biochemical parameters in the brain of γ-irradiated rats, which could be attributed to the enhancement of its antioxidant activity after fermentation. These findings suggested that fermentation enhances the protective effect of Gb in the brain on the neuroinflammation, release of the stress hormones, apoptosis and oxidative damage induced by γ-irradiation. fermentation improved the bio-activities of Gb leaf extract and thus enhanced the in-vivo antioxidant, anti-apoptotic and anti-inflammatory activities, leading to

  20. Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle.

    Science.gov (United States)

    Py, Guillaume; Eydoux, Nicolas; Lambert, Karen; Chapot, Rachel; Koulmann, Natahlie; Sanchez, Hervé; Bahi, Lahoucine; Peinnequin, André; Mercier, Jacques; Bigard, André-Xavier

    2005-05-01

    To dissect the independent effects of altitude-induced hypoxemia and anorexia on the capacity for cardiac lactate metabolism, we examined the effects of 21 days of chronic hypobaric hypoxia (CHH) and its associated decrease in food intake and right ventricle (RV) hypertrophy on the monocarboxylate transporter 1 and 4 (MCT) expression, the rate of lactate uptake into sarcolemmal vesicles, and the activity of lactate dehydrogenase isoforms in rat muscles. In comparison with control rats (C), 1 mmol/L lactate transport measured on skeletal muscle sarcolemmal vesicles increased by 33% and 58% in hypoxic (CHH, barometric pressure = 495 hPa) and rats pair-fed an equivalent quantity of food to that consumed by hypoxic animals, respectively. The increased lactate transport was higher in PF than in CHH animals ( P < .05). No associated change in the expression of MCT1 protein was observed in skeletal muscles, whereas MCT1 mRNA decreased in CHH rats, in comparison with C animals (42%, P < .05), partly related to caloric restriction (30%, P < .05). MCT4 mRNA and protein increased during acclimatization to hypoxia only in slow-oxidative muscles (68%, 72%, P < .05, respectively). The MCT4 protein content did not change in the plantaris muscle despite a decrease in transcript levels, related to hypoxia and caloric restriction. In both the left and right ventricles, the MCT1 protein content was unaffected by ambient hypoxia or restricted food consumption. These results suggest that MCT1 and MCT4 gene expression in fast-glycolytic muscles is mainly regulated by posttranscriptional mechanisms. Moreover, the results emphasize the role played by caloric restriction on the control of gene expression in response to chronic hypoxia and suggest that hypoxia-induced right ventricle hypertrophy failed to alter MCT proteins.

  1. Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production

    Directory of Open Access Journals (Sweden)

    Monteiro Priscila F

    2012-01-01

    Full Text Available Abstract Background Adiposity greatly increases the risk of atherothrombotic events, a pathological condition where a chronic state of oxidative stress is reported to play a major role. This study aimed to investigate the involvement of (NO-soluble guanylyl cyclase (sGC signaling pathway in the platelet dysfunction from high fat-fed (HFF rats. Methods Male Wistar rats were fed for 10 weeks with standard chow (SCD or high-fat diet (HFD. ADP (10 μM- and thrombin (100 mU/ml-induced washed platelet aggregation were evaluated. Measurement of intracellular levels of ROS levels was carried out using flow cytometry. Cyclic GMP levels were evaluated using ELISA kits. Results High-fat fed rats exhibited significant increases in body weight, epididymal fat, fasting glucose levels and glucose intolerance compared with SCD group. Platelet aggregation induced by ADP (n = 8 and thrombin from HFD rats (n = 8 were significantly greater (P n = 6. N-acetylcysteine (NAC; 1 mM and PEG-catalase (1000 U/ml fully prevented the increased ROS production and platelet hyperaggregability in HFD group. The NO donors sodium nitroprusside (SNP; 10 μM and SNAP (10 μM, as well as the NO-independent soluble guanylyl cyclase stimulator BAY 41-2272 (10 μM inhibited the platelet aggregation in HFD group with lower efficacy (P P n = 4. Conclusions Metabolic abnormalities as consequence of HFD cause platelet hyperaggregability involving enhanced intraplatelet ROS production and decreased NO bioavailability that appear to be accompanied by potential defects in the prosthetic haem group of soluble guanylyl cyclase.

  2. Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats.

    Science.gov (United States)

    Albayrak, Abdulmecit; Halici, Zekai; Cadirci, Elif; Polat, Beyzagul; Karakus, Emre; Bayir, Yasin; Unal, Deniz; Atasoy, Mustafa; Dogrul, Ahmet

    2013-09-05

    The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology.

  3. Role of extracellular signal-regulated kinase in regulating expression of interleukin 13 in lymphocytes from an asthmatic rat model

    Institute of Scientific and Technical Information of China (English)

    LI Yuan-yuan; LIU Xian-sheng; LIU Chang; XU Yong-jian; XIONG Wei-xing

    2010-01-01

    Background The extracellular signal-regulated kinase (ERK) is widely expressed in mammal cells and involved in airway proliferation and remodeling in asthma. In this study, we intend to explore the role of ERK in the expression of the Th2 cytokine, interleukin 13 (IL-13) in lymphocytes in asthma.Methods Forty Sprague-Dawley rats were randomly divided into two groups: normal control and asthmatic groups. Peripheral blood lymphocytes were isolated and purified from the blood of each rat and divided into five groups: control, asthmatic lymphocytes, asthmatic cells stimulated with ERK activator epidermal growth factor (EGF), or with ERK inhibitor PD98059, or with EGF and PD98059 together. The expression of phosphorylated-ERK (p-ERK) was observed by immunocvtochemical staining, the expression of ERK mRNA was determined by reverse transcriptase-PCR, IL-13 protein in supernatants was measured by ELISA.Results (1) The ERK mRNA level and the percentage of cells with p-ERK in lymphocytes from asthmatic rats were significantly higher than those in normal controls, and were significantly increased by EGF administration. This effect of EGF was significantly inhibited by PD98059 pretreatment. (2) IL-13 protein in supematants of asthmatic lymphocytes was higher than that produced by normal control lymphocytes, and was significantly increased by EGF treatment. This EGF effect was partly blocked by PD98059 pretreatment. (3) There was a significant positive correlation between the percentage of cells with p-ERK in peripheral blood lymphocytes and IL-13 protein in supematants of lymphocytes from asthmatic rats.Conclusions In asthma the ERK expression and activation levels were increased, as was the protein level of IL-13. The ERK signaling pathway may be involved in the increased expression of the Th2 cytokine IL-13 in asthma.

  4. Epigallocatechin gallate supplementation protects against renal injury induced by fluoride intoxication in rats: Role of Nrf2/HO-1 signaling

    Directory of Open Access Journals (Sweden)

    S. Thangapandiyan

    2014-01-01

    Full Text Available Fluoride intoxication generates free radicals, causing oxidative stress that plays a critical role in the progression of nephropathy. In the present study, we hypothesized that epigallocatechin gallate (EGCG, found in green tea, protects the kidneys of rats treated with fluoride by preventing oxidative stress, inflammation, and apoptosis. Pretreatment of fluoride-treated rats with EGCG resulted in a significant normalization of creatinine clearance and levels of urea, uric acid, and creatinine. Fluoride intoxication significantly increased renal oxidative stress markers and decreased the levels of renal enzymatic and non-enzymatic antioxidants. In addition, renal NO, TNF-α, IL-6 and NF-κB were also increased in the renal tissue of fluoride-treated rats. Further, EGCG pretreatment produced a significant improvement in renal antioxidant status and reduced lipid peroxidation, protein carbonylation and the levels of inflammatory markers in fluoride-treated kidney. Similarly, mRNA and protein analyses showed that EGCG pretreatment normalized the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in fluoride-treated rat kidney. EGCG also effectively attenuated fluoride-induced renal apoptosis by the up-regulation of anti-apoptotic proteins such as Bcl-2 and down-regulation of Bax, caspase-3, caspase-9 and cytochrome c. Histology and immunohistochemical observations of Kim-1 provided further evidence that EGCG effectively protects the kidney from fluoride-mediated oxidative damage. These results suggest that EGCG ameliorates fluoride-induced oxidative renal injury by activation of the Nrf2/HO-1 pathway.

  5. The role of miR-34a in the hepatoprotective effect of hydrogen sulfide on ischemia/reperfusion injury in young and old rats.

    Science.gov (United States)

    Huang, Xinli; Gao, Yun; Qin, Jianjie; Lu, Sen

    2014-01-01

    Hydrogen sulfide (H2S) can protect the liver against ischemia-reperfusion (I/R) injury. However, it is unknown whether H2S plays a role in the protection of hepatic I/R injury in both young and old patients. This study compared the protective effects of H2S in a rat model (young and old animals) of I/R injury and the mechanism underlying its effects. Young and old rats were assessed following an injection of NaHS. NaHS alone reduced hepatic I/R injury in the young rats by activating the nuclear erythroid-related factor 2 (Nrf2) signaling pathway, but it had little effect on the old rats. NaHS pretreatment decreased miR-34a expression in the hepatocytes of the young rats with hepatic I/R. Overexpression of miR-34a decreased Nrf-2 and its downstream target expression, impairing the hepatoprotective effect of H2S on the young rats. More importantly, downregulation of miR-34a expression increased Nrf-2 and the expression of its downstream targets, enhancing the effect of H2S on hepatic I/R injury in the old rats. This study reveals the different effects of H2S on hepatic I/R injury in young and old rats and sheds light on the involvement of H2S in miR-34a modulation of the Nrf-2 pathway.

  6. The role of chemokines in regualating mast cell recruitment around rat liver tumor

    Institute of Scientific and Technical Information of China (English)

    ZHANGZhi-Yong; RUANYou-Bing

    2001-01-01

    Aim To explore the correlation of stem cell factor (SCF)and monocyte chemoattractant protein-1 (MCP-1) with number difference of mast cell (MC) around the liver tumor.Methods 40 male wistar rats with liver neoplasm were divided into three different groups by numbers of MC in the surroundings of tumor. We performed ELISA for SCF and MCP-1 in serums. And chemotaxis assays of rat peritoneal MCs to SCF and MCP-1 in serums were measured in 48-wellmicroboyden chambers. We also used immunohistochemistryto investigate whether rat MCs express SCF positively.RESULTE There were marked differences in MC numbersaround tumor between different groups. The group that has more MCs around tumor has the higher levels of SCF andMCP-1 in serums and the stronger chemotaxis to ratperitoneal MCs. SCF washigher than MCP-1 in bothchemotactic activity to MCs and levels in serums. And ratMCs positively express SCF.Conclusion SCF and MCP-1 were found to be two particularly efficacious chemoattractants for MCs. The levels of SCF and MCP-1 in serums may be closely correlated with MCs numbers around tumor. The production of SCF by MCs might act on mast cell migration and proliferation of MC.

  7. Protective role of methylprednisolone and heparin in ischaemic-reperfusion injury of the rat testicle.

    Science.gov (United States)

    Mertoğlu, C; Senel, U; Cayli, S; Tas, U; Küskü Kiraz, Z; Özyurt, H

    2016-09-01

    This study evaluated the therapeutic efficacy of heparin and methylprednisolone in the treatment of ischaemic reperfusion (IR) injury of the testis. Twenty-four male Sprague-Dawley rats were allocated equally into three groups of eight animals each. The left testes were rotated 720° for 2 h in the rats in the torsion-detorsion group. Rats in the treatment groups underwent the same surgical procedure as the torsion-detorsion group but were also given methylprednisolone (group II) or heparin (group III) by an intraperitoneal route 30 min prior to detorsion. Left orchiectomy was performed in all rats from each experimental animal at 2 h after detorsion, and the tissue was harvested for the measurement of malondialdehyde (MDA), protein carbonyl (PC) and nitric oxide (NO) and the endogenous antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase. Additional tissue was evaluated using histopathological and immunohistochemical changes. PC and MDA levels were significantly reduced in the treated groups compared to the control group. There was no statistically significant difference in NO level or SOD, GSH-Px and catalase activity among the treatment groups. Histopathological and immunohistochemical findings supported biochemical changes. It is concluded that pre-treatment with methylprednisolone or heparin protects the testis in ischaemic reperfusion injury caused by testicular torsion-detorsion.

  8. Role of corticosterone on sleep homeostasis induced by REM sleep deprivation in rats.

    Science.gov (United States)

    Machado, Ricardo Borges; Tufik, Sergio; Suchecki, Deborah

    2013-01-01

    Sleep is regulated by humoral and homeostatic processes. If on one hand chronic elevation of stress hormones impair sleep, on the other hand, rapid eye movement (REM) sleep deprivation induces elevation of glucocorticoids and time of REM sleep during the recovery period. In the present study we sought to examine whether manipulations of corticosterone levels during REM sleep deprivation would alter the subsequent sleep rebound. Adult male Wistar rats were fit with electrodes for sleep monitoring and submitted to four days of REM sleep deprivation under repeated corticosterone or metyrapone (an inhibitor of corticosterone synthesis) administration. Sleep parameters were continuously recorded throughout the sleep deprivation period and during 3 days of sleep recovery. Plasma levels of adrenocorticotropic hormone and corticosterone were also evaluated. Metyrapone treatment prevented the elevation of corticosterone plasma levels induced by REM sleep deprivation, whereas corticosterone administration to REM sleep-deprived rats resulted in lower corticosterone levels than in non-sleep deprived rats. Nonetheless, both corticosterone and metyrapone administration led to several alterations on sleep homeostasis, including reductions in the amount of non-REM and REM sleep during the recovery period, although corticosterone increased delta activity (1.0-4.0 Hz) during REM sleep deprivation. Metyrapone treatment of REM sleep-deprived rats reduced the number of REM sleep episodes. In conclusion, reduction of corticosterone levels during REM sleep deprivation resulted in impairment of sleep rebound, suggesting that physiological elevation of corticosterone levels resulting from REM sleep deprivation is necessary for plentiful recovery of sleep after this stressful event.

  9. Role of capsaicin-sensitive nerve fibers in uterine contractility in the rat.

    Science.gov (United States)

    Klukovits, Anna; Gaspar, Robert; Santha, Peter; Jancso, Gabor; Falkay, George

    2004-01-01

    The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.

  10. The protective role of Gongronema latifolium in acetaminophen induced hepatic toxicity in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Nnodim Johnkennedy; Emejulu Adamma

    2011-01-01

    Objective: To evaluate the protective effect of leaf extract of Gongronema latifolium (G. latifolium) against acute acetaminophen induced hepatic toxicity in Wistar rats. Methods:Thirty six Wistar rats were divided into 6 groups with 6 rats in each group. Animals in group 1 and 2 were administered with 600 mg/kg b.w. of acetaminophen only and acetaminophen plus 100 mg/kg b.w. of caffeine by oral gavages, respectively. Experimental groups 3 and 4 were treated as in group 1 but in addition received 200 and 400 mg/kg b.w., respectively of the leaf extract of G. latifolium by oral gavages. The experimental groups 5 and 6 were treated as in group 2 and in addition received 200 and 400 mg/kg b.w. of leaf extract of G. latifolium, respectively. The treatment lasted for 14 days. Results: The results obtained showed that the serum glutamic-oxalacetic transaminease (AST), glutamic-pyruvic transaminase (ALT) and alkaline phosphatase (ALP) levels had a greater increase in group 2 than in group 1 but dropped marginally in groups 3 and 4. However, in groups 5 and 6, AST, ALT and ALP were significantly reduced (P<0.05). Similarly, serum protein levels were significantly increased in groups 3, 4, 5 and 6 when compared with group 1 and 2. Conclusions: It can be concluded that extract of G. latifolium offers protection against acetaminophen and caffeinated acetaminophen toxicity in Wistar rats.

  11. THE REGULATION OF DOPAMINE RELEASE FROM NIGROSTRIATAL NEURONS IN CONSCIOUS RATS - THE ROLE OF SOMATODENDRITIC AUTORECEPTORS

    NARCIS (Netherlands)

    SANTIAGO, M; WESTERINK, BHC

    1991-01-01

    Drugs were infused into the substantia nigra of the rat brain via a microdialysis probe, and the extracellular concentration of dopamine (DA) and 3,4-dihydroxyphenylacetic acid was recorded from a second dialysis probe implanted in the ipsilateral striatum. This approach allowed the evaluation of th

  12. A Signaling Role for Leptin in Puberty Onset in Female Rats?

    NARCIS (Netherlands)

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

    2006-01-01

    The brain might initiate puberty in response to adequate leptin signaling from the periphery. We studied the link between whole body fat, plasma leptin levels, and puberty onset, in both controls and food-restricted female Wistar rats from age 22 to 42 days. Body fat correlated positively with the p

  13. Role of KATP channels in the regulation of rat dura and pia artery diameter

    DEFF Research Database (Denmark)

    Gozalov, A.; Petersen, K.A.; Mortensen, C.;

    2005-01-01

    The aim of the present study was to examine the effect of K(ATP) channel openers pinacidil and levcromakalim on rat dural and pial arteries as well as their inhibition by glibenclamide. We used an in-vivo genuine closed cranial window model and an in-vitro organ bath. Glibenclamide alone reduced ...

  14. Lateral septal vasopressin in rats : Role in social and object recognition?

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM

    1997-01-01

    The capacity of male rats to remember familiar conspecifics is called social recognition. It is a form of short-term memory modulated by lateral septal (LS) vasopressin (VP). The specificity of this phenomenon was studied by examining whether recognition of previously investigated objects is also un

  15. A Signaling Role for Leptin in Puberty Onset in Female Rats?

    NARCIS (Netherlands)

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

    2006-01-01

    The brain might initiate puberty in response to adequate leptin signaling from the periphery. We studied the link between whole body fat, plasma leptin levels, and puberty onset, in both controls and food-restricted female Wistar rats from age 22 to 42 days. Body fat correlated positively with the

  16. The role of alkaloids in Ipomoea carnea toxicosis: a study in rats.

    Science.gov (United States)

    Hueza, Isis M; Guerra, José L; Haraguchi, Mitsue; Naoki, Asano; Górniak, Silvana L

    2005-08-01

    Ipomoea carnea promotes in livestock a toxicosis histologically characterized by vacuolated cells in different organs. The toxic principles of I. carnea are the alkaloids swainsonine and calystegines B1, B2, B3 and Cl. However, it has not been determined whether the effects observed in rats treated with this plant are only due to swainsonine or if the calystegines have some additive toxic effect. Thus, the aim of the present study was to evaluate in rats the toxic effects of the L carnea aqueous fraction (AF) and of its different alkaloids when administered individually at the same concentration as in this fraction, for 14 days. No anorexic effect and/or alteration in body weight was observed in any group. The histopathologic study showed that while calystegines did not produce any toxic effects, swainsonine and I carnea AF promoted vacuolation in different organs, being more severe in the animals from the I. carnea AF group and extensible to other organs evaluated. No alterations were detected in the central nervous system of rats of any group assayed. The results obtained here suggest that calystegines may act as coadjuvants of swainsonine in I carnea toxicosis; however, little can be proposed about the neurotoxic effect of I. carnea since rats did not prove to be a good model for the reproduction of neuronal storage disease.

  17. Role of noradrenaline in wake promotion effect of orexin-A on alcohol coma in rats

    Directory of Open Access Journals (Sweden)

    Tian-hao WANG

    2013-02-01

    Full Text Available Objective  To study whether or not noradrenaline system participates in the process of orexin-A wake-promoting from alcohol coma. Methods  Twenty-four adult female SPF SD rats were divided into four groups, 6 each, and the model of alcohol coma was reproduced. Experimental rats were then divided randomly into rats receiving injection of artificial cerebrospinal fluid (ACSF, control group, orexin-A (orexin-A group, noradrenaline α1 receptor antagonists--prazosin (prazosin group, or prazosin + orexin-A (prazosin-orexin-A group into the lateral ventricle. The depth of coma was evaluated by the duration of loss of righting reflex (LORR and δ wave in electrocorticogram (ECoG. Results  The duration of LORR was significantly longer and the ratio of δ wave higher in the prazosin-treated rats than those in control group (P0.05. But the values were significantly different from those in the orexin-A group (P<0.01. Conclusion  Noradrenaline system may participate in the wake-promoting process of alcohol coma by orexin-A.

  18. The Geometry of Conventionality

    CERN Document Server

    Weatherall, James Owen

    2013-01-01

    Hans Reichenbach famously argued that the geometry of spacetime is conventional in relativity theory, in the sense that one can freely choose the spacetime metric so long as one is willing to postulate a "universal force field". Here we make precise a sense in which the field Reichenbach defines fails to be a "force". We then argue that there is an interesting and perhaps tenable sense in which geometry is conventional in classical spacetimes. We conclude with a no-go result showing that the variety of conventionalism available in classical spacetimes does not extend to relativistic spacetimes.

  19. NO synthase uncoupling in the kidney of Dahl S rats: role of dihydrobiopterin.

    Science.gov (United States)

    Taylor, Norman E; Maier, Kristopher G; Roman, Richard J; Cowley, Allen W

    2006-12-01

    NO synthase (NOS) can paradoxically contribute to the production of reactive oxygen species when l-arginine or the cofactor R-tetrahydrobiopterin (BH(4)) becomes limited. The present study examined whether NOS contributes to superoxide production in kidneys of hypertensive Dahl salt-sensitive (SS) rats compared with an inbred consomic control strain (SS-13(BN)) and tested the hypothesis that elevated dihydrobiopterin (BH(2)) levels are importantly involved in this process. This was assessed by determining the effects of l-nitroarginine methyl ester (l-NAME) inhibition of NOS on superoxide production and by comparing tissue concentrations of BH(4) and BH(2). A reverse-phase high-performance liquid chromatography method was applied for direct measurements of BH(4) and BH(2) using (S)-tetrahydrobiopterin as an internal standard. Superoxide concentrations were measured in vivo from medullary microdialysis fluid using dihydroethidine and in vitro using lucigenin. The results indicate the following: (1) that superoxide levels were elevated in the outer medulla of SS rats fed a 4% salt diet and could be inhibited by l-NAME. In contrast, l-NAME resulted in elevated superoxide production in consomic SS-13(BN) rats because of higher NOS activity; (2) SS rats showed a reduced ratio of BH(4)/BH(2) in the outer medulla that was driven by increased concentrations of BH(2); and (3) lower superoxide dismutase and catalase activities contributed to elevated reactive oxygen species in SS samples. Based on the shift of BH(4) to BH(2) and the observation of l-NAME inhibitable superoxide production, we conclude that NOS uncoupling occurs in the renal medulla of hypertensive SS rats fed a high-salt diet.

  20. Lawyer of defendant and his role in the criminal process from the viewpoint of the European Convention on Human Rights and the Albanian criminal procedural legislation

    Directory of Open Access Journals (Sweden)

    Klodjan Skenderaj

    2014-01-01

    Full Text Available A guarantee for real ensuring of defendant’s rights is the qualified legal assistance by the side of the lawyer, chosen or assigned by the proceeding body. Providing legal protection to defendants was an important achievement in the long and difficult efforts to democratize the criminal proceedings. It was initially achieved in developed countries which promulgated the fundamental rights and freedoms and on this basis the major laws of activity of justice’s bodies were enforced. The role of lawyer in the criminal proceeding gradually increased and became an important factor in the fight against violations of law and injustice. The lawyer became a respected procedural figure, standing in front of prosecution, as the opposing party able to develop a cross-examination and to influence in a fair solution of case. However in practice, it is not rare the violation of rights of defendants by proceeding organs. So, it is right to make this question: What will be done with their rights and how will they be protected? In practice there were different opinions in terms of guaranteeing the rights of these defendants and how far the rights of lawyers of the defendants are extended. This is the reason why this paper will bring in attention the position, procedural guarantees of lawyers, the actions that can take and the exercise of their main rights in defending the interest of defendant, taking into account the main phases of criminal proceedings. Special attention will be devoted to case law of European Court of Human Rights (ECHR in terms of guaranteeing the rights of defendants, the orientations of the Albanian Constitutional Court and that of Supreme Court. At the end, this paper will reach in some conclusions through which proposals and amendments will be made to the code of criminal procedure, starting from the principle that the rights and procedural guarantees of defendants should be guaranteed at the maximum, because it’s the only way to

  1. Role of ghrelin on testosterone secretion and the mRNA expression of androgen receptors in adult rat testis.

    Science.gov (United States)

    Wang, Lin; Fang, Fugui; Li, Yunsheng; Zhang, Yunhai; Pu, Yong; Zhang, XiaoYong

    2011-06-01

    The present study was designed to determine the effects of ghrelin on in vivo and in vitro secretion of testosterone (T) and the expression of androgen receptor (AR) mRNA in the adult rat testis. The distribution of growth hormone secretagogue receptors (GHS-R(1a)) in the testis was also investigated. GHS-R(1a) immunoreactivity presented mainly in Sertoli and Leydig cells, primary spermatocytes, and secondary spermatocytes. Adult rats that were intracerebroventricularly (i.c.v.) administrated different dosages (1 nmol and 3 nmol) of ghrelin could significantly inhibit the secretion of T. The experession of AR mRNA in the testis was also notably reduced with 3 nmol ghrelin. Additionaly, in vitro exposure of the Leydig cells to increasing concentrations of ghrelin resulted in no obvious changes of T secretion in the culture media and AR mRNA expression of Leydig cells. Overall, our data demonstrate that the i.c.v. injection of ghrelin plays a physiological role in T secretion and AR mRNA expression in the testis, further confirming the reproductive role of ghrelin.

  2. Roles of NHE-1 in the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats

    Institute of Scientific and Technical Information of China (English)

    姚伟; 钱桂生; 杨晓静

    2002-01-01

    Objective To evaluate the roles of Na+/H+ exchanger-1 (NHE-1)in the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats. Methods Twenty Wistar rats were randomized into control group and 3-week hypoxic group. Intracellular pH (pHi) of the smooth muscle was determined with fluorescence measurement of the pH-sensitive dye BCECF-AM, and the expression of NHE-1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Primary culture of pulmonary artery smooth muscle cells in vitro was performed. In situ cell death detection kit (TUNEL) was used for studying the effect of specific NHE-1 inhibitor-dimethyl amiloride (DMA) on the apoptosis of muscle cells which had intracellular acidification. Results pHi value and NHE-1 mRNA expression of pulmonary artery smooth muscle cells were significantly higher in the hypoxic group than in the control group (P<0.01, P<0.001). DMA elevated the apoptotic ratio remarkably. The effect was enhanced when DMA concentration increased and the time prolonged. Conclusions With the function of adjusting pHi, NHE-1 may play an important role in the proliferation and apoptosis of pulmonary artery smooth muscle cells.

  3. Role of neuronal nitric oxide synthase and inducible nitric oxide synthase in intestinal injury in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Hui LU; Bing Zhu; Xin-Dong Xue

    2006-01-01

    AIM: To investigate the dynamic change and role of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in neonatal rat with intestinal injury and to define whether necrotizing enterocolitis (NEC) is associated with the levels of nitric oxide synthase (NOS) in the mucosa of the affected intestine tissue.METHODS: Wistar rats less than 24 h in age received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileum tissues were collected at 1, 3, 6, 12 and 24 h following LPS challenge for histological evaluation of NEC and for measurements of nNOS and iNOS. The correlation between the degree of intestinal injury and levels of NOS was determined.RESULTS: The LPS-injected pups showed a significant increase in injury scores versus the control. The expression of nNOS protein and mRNA was diminished after LPS injection. There was a negative significant correlation between the nNOS protein and the grade of median intestinal injury within 24 h. The expression of iNOS protein and mRNA was significantly increased in the peak of intestinal injury.CONCLUSION: nNOS and iNOS play different roles in LPS-induced intestinal injury. Caution should be exerted concerning potential therapeutic uses of NOS inhibitors in NEC.

  4. Conventional Spinal Anaesthesia

    African Journals Online (AJOL)

    patients scheduled for clcctive unilateral lower limb surgery. ... the conventional group were turned supine immediately after injection. Blood pressure, heart rate, respiratory rate and oxygen .... Characteristic Type of spinal anaesthcsia P-value.

  5. Characterization of the Rat GAL2R Promoter: Positive Role of ETS-1 in Regulation of the Rat GAL2R Gene in PC12 Cells.

    Science.gov (United States)

    Yang, Yutao; Liu, Li; Luo, Hanjiang; Li, Yueting; Li, Hui; Xu, Zhi-Qing David

    2017-08-01

    Galanin receptor 2 (GAL2R) is a G protein-coupled receptor for the neuropeptide galanin that regulates many important physiological functions and pathological processes. To investigate the molecular mechanism governing GAL2R gene transcription, the rat GAL2R promoter was isolated and analyzed. We found that the region from -320 to -300 of the GAL2R promoter contains two putative ETS-1 elements and plays an important role in regulating GAL2R promoter activity. We also showed that transcription factor ETS-1 bound to this region in vitro and in vivo. Overexpression of ETS-1 significantly increased GAL2R promoter activity and transcription of the GAL2R gene, whereas knockdown of ETS-1 produced the opposite effects. In addition, we showed that ETS-1 recruited co-activator p300 to the GAL2R promoter. These data indicate a role for ETS-1 in the control of the GAL2R gene expression and provide a basis for understanding the transcriptional regulation of the GAL2R gene.

  6. The role of dietary fatty acids in predicting myocardial structure in fat-fed rats

    Directory of Open Access Journals (Sweden)

    Miller Melissa L

    2011-06-01

    Full Text Available Abstract Background Obesity increases the risk for development of cardiomyopathy in the absence of hypertension, diabetes or myocardial ischemia. Not all obese individuals, however, progress to heart failure. Indeed, obesity may provide protection from cardiovascular mortality in some populations. The fatty acid milieu, modulated by diet, may modify obesity-induced myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy in obese individuals. Methods Adult male Sprague-Dawley rats were fed 1 of the following 4 diets for 32 weeks: control (CON; 50% saturated fat (SAT; 40% saturated fat + 10% linoleic acid (SAT+LA; 40% saturated fat + 10% α-linolenic acid (SAT+ALA. Serum leptin, insulin, glucose, free fatty acids and triglycerides were quantitated. In vivo cardiovascular outcomes included blood pressure, heart rate and echocardiographic measurements of structure and function. The rats were sacrificed and myocardium was processed for fatty acid analysis (TLC-GC, and evaluation of potential modifiers of myocardial structure including collagen (Masson's trichrome, hydroxyproline quantitation, lipid (Oil Red O, triglyceride quantitation and myocyte cross sectional area. Results Rats fed SAT+LA and SAT+ALA diets had greater cranial LV wall thickness compared to rats fed CON and SAT diets, in the absence of hypertension or apparent insulin resistance. Treatment was not associated with changes in myocardial function. Myocardial collagen and triglycerides were similar among treatment groups; however, rats fed the high-fat diets, regardless of composition, demonstrated increased myocyte cross sectional area. Conclusions Under conditions of high-fat feeding, replacement of 10% saturated fat with either LA or ALA is associated with thickening of the cranial LV wall, but without concomitant functional changes. Increased myocyte size appears to be a more likely contributor to early LV thickening in response to

  7. Haematotoxic and reproductive toxicity of fixed dose combined anti-tuberculous agents: protective role of antioxidants in rats.

    Science.gov (United States)

    Awodele, O; Osunkalu, V O; Adejumo, I A; Odeyemi, A A; Ebuehi, O A T; Akintonwa, A

    2013-01-01

    Tuberculosis (TB) is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS. The major problem militating against the management of tuberculosis is the lack of compliance to medication by the infected patients as a result of multidrug needed to be taking daily leading to resistance. Occurrences of hepatic toxicity, teratogenicity, sperm quality damage, haematotoxicity and meningeal congestion of individual anti-tuberculous agents have been reported. The study is aimed to determine the reproductive and haematological toxicity of combined antituberculous agents and the modulatory role of antioxidants using animal model. Fifty rats (10 per group) were randomly allotted to five groups, consisting of the control, the fixed dose combined anti TB agents treated group, the fixed dose combined anti TB agents plus vitamin C treated group, the fixed dose combined anti TB agents plus vitamin E treated group and the fixed dose combined anti TB agents plus vitamin C plus vitamin E treated group. Therapeutic doses of the fixed dose combined anti TB agents (25 mg/kg/day), vitamin E (5 mg/kg) and vitamin C (8 mg/kg) were administered to the animals via oral gavage, daily over 28 days. After 28days, rats were sacrificed for internal macroscopic and histological examination of the organs, sperm analysis and haematological investigations were carried out. The results showed a significant increase (p < or = 0.05) in the levels of white blood cells (WBC), red blood cell (RBC) and haemoglobin (HB) of the combined anti-TB plus vitamins C or E treated groups compared with combined anti-TB treated group alone (56.34 +/- 0.11) that decreased the haematological parameters. A significant decrease (p < or = 0.05) in the sperm counts (22.26 +/- 0.02; 35.40 +/- 0.02) and motility (77.03 +/- 0.02; 94.50 +/- 0.01) of the combined anti-TB treated rats as compared with the control group were observed. The combined anti-TB plus

  8. Protective role of melatonin in domoic acid-induced neuronal damage in the hippocampus of adult rats.

    Science.gov (United States)

    Ananth, C; Gopalakrishnakone, P; Kaur, C

    2003-01-01

    Domoic acid (DA), a kainite-receptor agonist and potent inducer of neurotoxicity, has been administered intravenously in adult rats in the present study (0.75 mg/kg body weight) to demonstrate neuronal degeneration followed by glial activation and their involvement with inducible nitric oxide synthase (iNOS) in the hippocampus. An equal volume of normal saline was administered in control rats. The pineal hormone melatonin, which protects the neurons efficiently against excitotoxicity mediated by sensitive glutamate receptor, was administered intraperitoneally (10 mg/kg body weight), 20 min before, immediately after, and 1 h and 2 h after the DA administration, to demonstrate its role in therapeutic strategy. Histopathological analysis (Nissl staining) demonstrated extensive neuronal damage in the pyramidal neurons of CA1, CA3 subfields and hilus of the dentate gyrus (DG) in the hippocampus at 5 days after DA administration. Sparsely distributed glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were observed in the hippocampus at 4-24 h after DA administration and in the control rats. Astrogliosis was evidenced by increased GFAP immunoreactivity in the areas of severe neuronal degeneration at 5 days after DA administration. Along with this, microglial cells exhibited an intense immunoreaction with OX-42, indicating upregulation of complement type 3 receptors (CR3). Ultrastructural study revealed swollen or shrunken degenerating neurons in the CA1, CA3 subfields and hilus of the DG and hypertrophied astrocytes showing accumulation of intermediate filament bundles in the cytoplasm were observed after administration of DA. Although no significant change could be observed in the mRNA level of iNOS expression between the DA-treated rats and controls at 4-24 h and at 5-day time intervals, double immunofluorescense revealed co-expression of induced iNOS with GFAP immunoreactive astrocytes, but not in the microglial cells, and iNOS expression in the neurons

  9. Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin?

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    Juliana C Ferreira

    Full Text Available High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx and total parathyroidectomy (PTx were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH and fibroblast growth factor 23 (FGF23 levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV, higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might

  10. Critical role of NMDA but not opioid receptors in the acquisition of fat-conditioned flavor preferences in rats.

    Science.gov (United States)

    Dela Cruz, J A D; Bae, V S; Icaza-Cukali, D; Sampson, C; Bamshad, D; Samra, A; Singh, S; Khalifa, N; Touzani, K; Sclafani, A; Bodnar, R J

    2012-11-01

    Animals learn to prefer flavors associated with the intake of dietary fats such as corn oil (CO) solutions. We previously reported that fat-conditioned flavor preferences in rats were relatively unaffected by systemic treatment with dopamine D1 and D2 antagonsits. The present study examined whether systemic opioid (naltrexone, NTX) or NMDA (MK-801) receptor antagonists altered the acquisition and/or expression of CO-CFP. The CFP was produced by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in a 3.5% CO solution and another flavor (CS-, e.g., grape) in a 0.9% CO solution. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 d. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5h after systemic administration of vehicle (VEH), NTX (0.1-5 mg/kg) or MK-801 (50-200 μg/kg). Rats displayed a robust CS+ preference following VEH treatment (85-88%) which was significantly though moderately attenuated by NTX (69-70%). The lower doses of MK-801 slightly reduced the CS+ preference; the high dose blocked the CS+ preference (49%) but also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH or NTX (0.1, 0.5, 1mg/kg) or MK-801 (100 μg/kg) 0.5h prior to 1-bottle training trials with CS+/3.5% CO and CS-/0.9% CO training solutions. Additional Limited VEH groups were trained with intakes limited to that of the NTX and MK-801 groups. Subsequent two-bottle CS+ vs. CS- tests were conducted without injections. Significant and persistent CS+ preferences were observed in VEH (77-84%) and Limited VEH (88%) groups. NTX treatment during training failed to block the acquisition of CO-CFP although the magnitude of the CS+ preference was reduced by 0.5 (70%) and 1.0 (72%) mg/kg doses relative to the Limited VEH treatment (88%). In contrast, MK-801 (100 μg/kg) treatment during training blocked the acquisition of the CO-CFP. These data suggest a

  11. Decreased expression of GLUT4 in male CG-IUGR rats may play a vital role in their increased susceptibility to diabetes mellitus in adulthood.

    Science.gov (United States)

    Duan, Chang; Liu, Min; Xu, Haiyan; Tang, Weiwei; Liu, Jiayun; Hou, Lamei; Li, Lijuan

    2016-10-01

    Rats with intrauterine growth retardation and catch-up growth (CG-IUGR) after birth show increased susceptibility to diabetes mellitus in adulthood. The expression of glucose transporter type 4 (GLUT4) decreases in female IUGR offspring rats with seminutrient restriction during pregnancy. However, the male CG-IUGR rats also display an increased susceptibility to diabetes mellitus in adulthood. Whether there is another factor, besides GLUT4, in male CG-IUGR rat that mediates their susceptibility to diabetes mellitus? The male IUGR rats with catch-up growth were selected as the research objects. CG-IUGR rats had an increased fasting blood glucose level, and increased serum total cholesterol, triglyceride and free fatty acid levels. Glucose tolerance test and insulin tolerance test showed higher glucose levels and much higher insulin levels after a glucose load in CG-IUGR. The mRNA and protein expressions of IRS-2 in liver tissue, and IRS-1 and GLUT4 in skeletal muscle in CG-IUGR rats were down-regulated, but only the GLUT4 down-regulation displayed strong negative correlations with the decreased glucose tolerance capability by Pearson's analysis. The methylation patterns of CpG islands in the promoter regions of IRS-1, IRS-2 and GLUT4 in CG-IUGR rats varied, which was not significantly correlated with their expressions. The male CG-IUGR rats showed decreased glucose tolerant capability, suggesting increased susceptibility to diabetes mellitus in adulthood. The GLUT4 down-regulation may play a vital role in the development of decreased glucose tolerance in male CG-IUGR rats. The methylation modification of the promoter region of GLUT4 does not appear to be involved in its expression.

  12. Evidence for mobile phone radiation exposure effects on reproductive pattern of male rats: role of ROS.

    Science.gov (United States)

    Kesari, Kavindra Kumar; Behari, Jitendra

    2012-09-01

    The relationship between radiofrequency electromagnetic fields emitted from mobile phone and infertility is a matter of continuing debate. It is postulated that these radiations may affect the reproduction pattern spell by targeting biochemistry of sperm. In an attempt to expedite the issue, 70 days old Wistar rats (n = 6) were exposed to mobile phone radiofrequency (RF) radiation for 2 h per day for 45 days and data compared with sham exposed (n = 6) group. A significant decrease (P rats showed significant decreases in number and weight as compared with that of sham-exposed animals. A reduction in testosterone, an increase in caspase-3, and distortion in spermatozoa could be caused by overproduction of reactive oxygen species (ROS) in animals under mobile phone radiation exposure. Our findings on these biomarkers are clear indications of possible health implications of repeated exposure to mobile phone radiation.

  13. Antiproliferative role of Indigofera aspalathoides on 20 methylcholanthrene induced fibrosarcoma in rats

    Institute of Scientific and Technical Information of China (English)

    Sivagnanam Selva Kumar; Mudiganti Ram Krishna Rao

    2012-01-01

    Objective: To find out the anticancer effect of Indigofera aspalathoides (I. aspalathoides) on 20-methylcholanthrene induced fibrosarcoma in rats. Methods:Fibrosarcoma was induced in Wistar strain male albino rats by 20-methylcholanthrene. Intraperitoneous (i.p.) administration of 250 mg/kg body weight/day of aqueous extract of I. aspalathoides for 30 d effectively suppressed chemically induced tumors. Parameters such as body weight, liver and kidney weight, tumor weight, mean survival time, behavioral changes, blood glucose, blood glycogen and marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP) and 5'-nucleiotidase (5'-NT) in serum, liver and kidney and lipid profiles such as total cholesterol, phospholipids, free fatty acids in liver and kidney of control and experimental animals were studied. Results:Fibrosarcoma bearing animals were ferocious and anxious. The mean survival time was found to increase after the treatment. The body weights were significantly decreased (P<0.001) in group II fibrosarcoma animals which steadily increased after the treatment with I. aspalathoides. The liver and kidney weights were significantly increased whereas the tumor weights decreased as compared to the weights in untreated fibrosarcoma bearing rats. The blood glucose and the liver and kidney glycogen levels were found to decrease significantly (P<0.001) in group II animals. Elevated activities of marker enzymes were observed in serum, liver and kidney of fibrosarcoma bearing Group II animals which were normalize after I. aspalathoides treatment. In the liver and kidney of Group II animals the total cholesterol increased whereas the phospholipids and free fatty acid levels decreased (P<0.001) which were normalized after treatment. Conclusions:The treatment by I. aspalathoides on fibrosarcoma bearing rats has improved the levels of various parameters indicating its antiproliferative and

  14. Pleiotropic protective roles of melatonin against aluminium-induced toxicity in rats.

    Science.gov (United States)

    Allagui, Mohamed S; Hachani, Rafik; Saidi, Saber; Feriani, Anouer; Murat, Jean C; Kacem, Kamel; El feki, Abdelfatteh

    2015-10-01

    This study aimed to investigate the potential effects of melatonin on aluminium-induced toxicity in a rat model using a set of biochemical, inflammatory, oxidant, lipid profile criteria and hepatic integrity (verified by hematoxylin-eosin staining). The results indicated that AlCl3 administration during 60 days (100 mg/kg b.w.) significantly increased the activities of transaminases AST and ALT by 46% (p aluminium-intoxication.

  15. Chronic lead exposure decreases the vascular reactivity of rat aortas: the role of hydrogen peroxide.

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    Karolini Zuqui Nunes

    Full Text Available We investigated whether exposure to small concentrations of lead alters blood pressure and vascular reactivity. Male Wistar rats were sorted randomly into the following two groups: control (Ct and treatment with 100 ppm of lead (Pb, which was added to drinking water, for 30 days. Systolic blood pressure (BP was measured weekly. Following treatment, aortic ring vascular reactivity was assessed. Tissue samples were properly stored for further biochemical investigation. The lead concentration in the blood reached approximately 8 μg/dL. Treatment increased blood pressure and decreased the contractile responses of the aortic rings to phenylephrine (1 nM-100 mM. Following N-nitro-L arginine methyl ester (L-NAME administration, contractile responses increased in both groups but did not differ significantly between them. Lead effects on Rmax were decreased compared to control subjects following superoxide dismutase (SOD administration. Catalase, diethyldithiocarbamic acid (DETCA, and apocynin increased the vasoconstrictor response induced by phenylephrine in the aortas of lead-treated rats but did not increase the vasoconstrictor response in the aortas of untreated rats. Tetraethylammonium (TEA potentiated the vasoconstrictor response induced by phenylephrine in aortic segments in both groups, but these effects were greater in lead-treated rats. The co-incubation of TEA and catalase abolished the vasodilatory effect noted in the lead group. The present study is the first to demonstrate that blood lead concentrations well below the values established by international legislation increased blood pressure and decreased phenylephrine-induced vascular reactivity. The latter effect was associated with oxidative stress, specifically oxidative stress induced via increases in hydrogen peroxide levels and the subsequent effects of hydrogen peroxide on potassium channels.

  16. Antihypertensive responses elicited by central moxonidine in rats: Possible role of nitric oxide

    OpenAIRE

    Moreira, Thiago Santos [UNIFESP; Takakura, Ana Carolina Thomaz [UNIFESP; Sato, Monica Akemi; Menani, Jose Vanderlei; Colombari, Eduardo

    2006-01-01

    In the present study, we investigated the effects of pretreatment with N-G-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) injected intravenously (IV) on the hypotension, bradycardia, and vasodilation produced by moxonidine (alpha(2)-adrenergic/imidazoline receptor agonist) injected into the fourth brain ventricle (4th V) in rats submitted to acute hypertension that results from baroreflex blockade by bilateral injections of kynurenic acid (kyn, glutamatergic receptor...

  17. Furan toxicity on testes and protective role of lycopene in diabetic rats

    Science.gov (United States)

    Kara, Özlem; Baş, Hatice; Pandır, Dilek

    2016-01-01

    Objective Furan (C4H4O) is a heat-induced food contaminant that is utilized as an industrial chemical agent. Lycopene is a natural substance that is produced by plants and tomatoes. We aimed to evaluate the toxicity of furan on testes and the protective effect of lycopene in diabetic rats. Material and Methods Male Wistar albino rats were divided into five groups: Group 1 (control group) received 1 mL/kg corn oil. Group 2 (diabetic control group) received 55 mg/kg STZ and 1 mL/kg corn oil. Group 3 (diabetic lycopene group) received 55 mg/kg STZ and 4 mg/kg lycopene. Group 4 (diabetic furan group) received 55 mg/kg STZ and 40 mg/kg furan. Group 5 (diabetic furan + lycopene group) received 55 mg/kg STZ, 40 mg/kg furan, and 4 mg/kg lycopene. After 28 days, the testes were extirpated in all groups. In the testicular tissue samples, the level of malondialdehyde (MDA) and the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and reducted glutathione (GST) were studied. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were measured. Histopathologic examination was performed by light microscope. Results The MDA level and the activities of CAT, GPx, SOD, and GST were found to be higher in the furan group than in the control and diabetic control groups (p<0.05). The MDA level and the activities of CAT, GPx, SOD, and GST were significantly lower in the furan + lycopene group than in the furan group (p<0.05). Conclusion The low blood testosterone level in the rats who received furan suggested the presence of endocrinological defects and cellular degenerative changes. Lycopene may be effective to reverse furan toxicity in diabetic rat testes. PMID:27990087

  18. Role of corticosterone on sleep homeostasis induced by REM sleep deprivation in rats.

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    Ricardo Borges Machado

    Full Text Available Sleep is regulated by humoral and homeostatic processes. If on one hand chronic elevation of stress hormones impair sleep, on the other hand, rapid eye movement (REM sleep deprivation induces elevation of glucocorticoids and time of REM sleep during the recovery period. In the present study we sought to examine whether manipulations of corticosterone levels during REM sleep deprivation would alter the subsequent sleep rebound. Adult male Wistar rats were fit with electrodes for sleep monitoring and submitted to four days of REM sleep deprivation under repeated corticosterone or metyrapone (an inhibitor of corticosterone synthesis administration. Sleep parameters were continuously recorded throughout the sleep deprivation period and during 3 days of sleep recovery. Plasma levels of adrenocorticotropic hormone and corticosterone were also evaluated. Metyrapone treatment prevented the elevation of corticosterone plasma levels induced by REM sleep deprivation, whereas corticosterone administration to REM sleep-deprived rats resulted in lower corticosterone levels than in non-sleep deprived rats. Nonetheless, both corticosterone and metyrapone administration led to several alterations on sleep homeostasis, including reductions in the amount of non-REM and REM sleep during the recovery period, although corticosterone increased delta activity (1.0-4.0 Hz during REM sleep deprivation. Metyrapone treatment of REM sleep-deprived rats reduced the number of REM sleep episodes. In conclusion, reduction of corticosterone levels during REM sleep deprivation resulted in impairment of sleep rebound, suggesting that physiological elevation of corticosterone levels resulting from REM sleep deprivation is necessary for plentiful recovery of sleep after this stressful event.

  19. Endometriosis-Induced Vaginal Hyperalgesia in the Rat: Role of the Ectopic Growths and their Innervation

    OpenAIRE

    McAllister, Stacy L.; McGinty, Kristina A.; Resuehr, David; Berkley, Karen J

    2009-01-01

    Endometriosis is a painful disorder defined by extrauteral endometrial growths whose contribution to pain symptoms is poorly understood. Endometriosis is created in rats by autotransplanting on abdominal arteries pieces of either uterus (ENDO), which form cysts, or fat (shamENDO), which do not form cysts. ENDO, but not shamENDO induces vaginal hyperalgesia. We tested the hypothesis that the cysts are necessary to maintain vaginal hyperalgesia by assessing the effect of surgically removing the...

  20. The role of apoptosis in early embryonic development of the adenohypophysis in rats

    OpenAIRE

    Gedrange Tomas; Kleinheinz Johannes; Driemel Oliver; Faltermeier Andreas; Lotz Kristina; Weingärtner Jens; Proff Peter

    2008-01-01

    Abstract Background Apoptosis is involved in fundamental processes of life, like embryonic development, tissue homeostasis, or immune defense. Defects in apoptosis cause or contribute to developmental malformation, cancer, and degenerative disorders. Methods The developing adenohypophysis area of rat fetuses was studied at the embryonic stage 13.5 (gestational day) for apoptotic and proliferative cell activities using histological serial sections. Results A high cell proliferation rate was ob...

  1. Cyclosporin inhibits hyperalgesia and edema in arthritic rats: role of the central nervous system

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    J.N. Francischi

    1997-01-01

    Full Text Available Since arthritis induced by Mycobacterium products (adjuvant in rats is considered to be immunologically driven, the objective of the present study was to determine if the immunosuppressor drug cyclosporin could affect hindpaw edema and joint hyperalgesia simultaneously. Female Holtzman rats (140-170 g presented hyperalgesia and edema on the 8th and 12th day following adjuvant injection. Daily systemic (oral or intramuscular administration of cyclosporin (0.5-5.0 mg kg-1 day-1 or dexamethasone (0.01-0.1 mg kg-1 day-1 for 15 days starting on day zero dose-dependently inhibited the hindpaw edema and hyperalgesia in arthritic rats. However, hyperalgesia but not edema could be detected two days after cyclosporin withdrawal. We concluded that a the continuous presence of cyclosporin is essential to reduce the development of joint hyperalgesia and that b different mechanisms underlie the appearance of hyperalgesia and edema in this model. The intracerebroventricular (icv administration of 5-50-fold smaller doses of cyclosporin (1.5-150 µg/day or dexamethasone (15 µg/day also reduced the arthritic hindpaw edema and hyperalgesia. Peripheral blood from animals injected with effective systemic cyclosporin doses showed detectable levels of the drug, whereas peripheral blood from those injected with icv cyclosporin did not, as measured by specific RIA. Our results indicate that cyclosporin administered by the central route is as effective as by the systemic route to reduce joint hyperalgesia and hindpaw edema in arthritic rats. The antiarthritic effect induced by low doses of cyclosporin in the central nervous system (CNS could be explored to avoid its often associated systemic side effects during chronic therapy. However, the mechanism(s involved in the antiarthritic response to cyclosporin in the CNS remain to be elucidated

  2. Role of nicotine on cognitive and behavioral deficits in sepsis-surviving rats.

    Science.gov (United States)

    Leite, Franco B; Prediger, Rui D; Silva, Mônica V; de Sousa, João Batista; Carneiro, Fabiana P; Gasbarri, Antonella; Tomaz, Carlos; Queiroz, Amadeu J; Martins, Natália T; Ferreira, Vania M

    2013-04-24

    Sepsis and its complications are important causes of mortality in intensive care units and sepsis survivors may present long-term cognitive and emotional impairments, including memory deficits and anxiety symptoms. In the present study, we investigated whether repeated nicotine administration can affect the behavioral changes in sepsis-surviving rats. Male Wistar rats were divided in two groups: sham-operated and experimental sepsis induced by cecal ligation and puncture (CLP). The animals were injected subcutaneously with nicotine (0.1 mg/kg) or vehicle once a day during 1 week before and/or 1 week after sepsis induction. Thirty minutes after the last administration (i.e., 7 days after surgery), the animals were tested in the open field, elevated plus-maze and step-down inhibitory avoidance tasks. The repeated nicotine treatment did not affect the survival rate in the sepsis group (50%). Moreover, no significant changes on locomotor activity were observed in the sepsis group while the treatment with nicotine during 1 week after surgery reduced the locomotion of sepsis-surviving rats in the open field. It is important to note that both schedules of nicotine treatment (prior and/or after CLP) improved the sepsis-induced anxiogenic-like responses. Interestingly, nicotine was able to improve short- and long-term inhibitory avoidance memory impairments, observed in sepsis survivors, only when administered during 2 consecutive weeks (i.e., prior and after CLP). Taken together, these results indicate that repeated nicotine administration does not alter the survival rate in rats submitted to CLP and provide new evidence that nicotine can improve long-lasting memory impairments and anxiogenic-like responses in sepsis-surviving animals.

  3. Role of quercetin and arginine in ameliorating nano zinc oxide-induced nephrotoxicity in rats

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    Faddah Laila M

    2012-05-01

    Full Text Available Abstract Background Nanoparticles are small-scale substances ( Method ZnO nanoparticles were administered orally in two doses (either 600 mg or 1 g/Kg body weight/day for 5 conscutive days to Wister albino rats. In order to detect the protective effects of the studied antioxidants against n-ZnO induced nepherotoxicity, different biochemical parameters were investigated. Moreover, histopathological examination of kidney tissue was performed. Results Nano zinc oxide-induced nephrotoxicity was confirmed by the elevation in serum inflammatory markers including: tumor necrosis factor alpha (TNF-α, interleukin-6 (IL-6; and C-reactive protein (CRP. Moreover, immunoglobulin (IGg, vascular endothelium growth factor (VEGF, and nitric oxide (NO were significantly increased in rat serum. Serum urea and creatinine levels were also significantly increased in rats intoxicated with n-ZnO particles compared with the control group. Additionally, a significant decrease in the non-enzymatic antioxidant reduced glutathione (GSH was shown in kidney tissues and serum glucose levels were increased. These biochemical findings were supported by a histopathological examination of kidney tissues, which showed that in the animals that received a high dose of n-ZnO, numerous kidney glomeruli underwent atrophy and fragmentation. Moreover, the renal tubules showed epithelial desquamation, degeneration and necrosis. Some renal tubules showed casts in their lumina. Severe congestion was also observed in renal interstitium. These effects were dose dependent. Cotreatment of rats with Qur and/or Arg along with n-ZnO significantly improved most of the deviated tested parameters. Conclusions The data show that Qur has a beneficial effect against n-ZnO oxidative stress and related vascular complications. Also, its combination with Arg proved to be even more effective in ameliorating nano zinc oxide nephrotoxicity.

  4. The role of the World Trade Organization and the 'three sisters' (the World Organisation for Animal Health, the International Plant Protection Convention and the Codex Alimentarius Commission) in the control of invasive alien species and the preservation of biodiversity.

    Science.gov (United States)

    Kahn, S; Pelgrim, W

    2010-08-01

    The missions of the World Organisation for Animal Health (OIE) include the design of surveillance and control methods for infectious transboundary animal diseases (including zoonoses), the provision of guarantees concerning animal health and animal production food safety, and the setting of standards for, and promotion of, animal welfare. The OIE role in setting standards for the sanitary safety of international trade in animals and animal products is formally recognised in the World Trade Organization (WTO) Agreement on the Application of Sanitary and Phytosanitary Measures (the SPS Agreement). While the primary focus of the OIE is on animal diseases and zoonoses, the OIE has also been working within the WTO framework to examine possible contributions the organisation can make to achieving the goals of the Convention on Biological Diversity, particularly to preventing the global spread of invasive alien species (IAS). However, at the present time, setting standards for invasive species (other than those connected to the cause and distribution of diseases listed by the OIE) is outside the OIE mandate. Any future expansion of the OIE mandate would need to be decided by its Members and resources (expertise and financial contributions) for an extended standard-setting work programme secured. The other international standard-setting organisations referenced by the SPS Agreement are the International Plant Protection Convention (IPPC) and the Codex Alimentarius Commission (CAC). The IPPC mandate and work programme address IAS and the protection of biodiversity. The CAC is not involved in this field.

  5. The protective role of pomegranate juice against carbon tetrachloride-induced oxidative stress in rats.

    Science.gov (United States)

    Pirinççioğlu, Mihdiye; Kızıl, Göksel; Kızıl, Murat; Kanay, Zeki; Ketani, Aydın

    2014-11-01

    Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study was carried out to determine the phenolic and flavonoid contents of Derik pomegranate juice and determine its effect against carbon tetrachloride (CCl4)-induced toxicity in rats. Animals were divided into four groups (n = 6): group I: control, group II: CCl4 (1 ml/kg), group III: CCl4 + pomegranate juice and group IV: CCl4 + ursodeoxycholic acid (UDCA). Treatment duration was 4 weeks, and the dose of CCl4 was administered once a week to groups II, III and IV during the experimental period. CCl4-treated rats caused a significant increase in serum enzyme levels, such as aspartate aminotransferase, alanine aminotransferase and total bilirubin, and decrease in albumin, when compared with control. Administration of CCl4 along with pomegranate juice or UDCA significantly reduces these changes. Analysis of lipid peroxide (LPO) levels by thiobarbutiric acid reaction showed a significant increase in liver, kidney and brain tissues of CCl4-treated rats. However, both pomegranate juice and UDCA prevented the increase in LPO level. Histopathological reports also revealed that there is a regenerative activity in the liver and kidney cells. Derik pomegranate juice showed to be hepatoprotective against CCl4-induced hepatic injury. In conclusion, present study reveals a biological evidence that supports the use of pomegranate juice in the treatment of chemical-induced hepatotoxicity.

  6. Cryogenic role of central endogenous hydrogen sulfide in the rat model of endotoxic shock.

    Science.gov (United States)

    Fernández, Rodrigo A R; Soriano, Renato N; Francescato, Heloísa D C; Sabino, João P; Coimbra, Terezila M; Branco, Luiz G S

    2016-11-01

    Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine β-synthase (CBS - responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D2 (PGD2) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H2S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2 production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

    Science.gov (United States)

    Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

    1986-01-01

    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

  8. Modulatory Role of Simvastatin against Aluminium Chloride-Induced Behavioural and Biochemical Changes in Rats

    Science.gov (United States)

    Nampoothiri, Madhavan; John, Jessy; Kumar, Nitesh; Mudgal, Jayesh; Nampurath, Gopalan Kutty; Chamallamudi, Mallikarjuna Rao

    2015-01-01

    Objectives. Aluminium, a neurotoxic agent in humans, has been implicated in the pathogenesis of neurodegenerative disorders. In this study, we examined the behavioral and biochemical effects of aluminium in rats with special emphasis on memory centres, namely, hippocampus and frontal cortex. Further, the effect of simvastatin treatment on aluminium intoxication was evaluated. Methods. Rats were exposed to aluminium chloride (AlCl3) for 60 days. Simvastatin (10 mg/kg/p.o.) and rivastigmine (1 mg/kg/p.o.) were administered daily prior to AlCl3. Behavioral parameters were assessed using Morris water maze test and actophotometer followed by biochemical investigations, namely, acetylcholinesterase (AChE) activity, TNF-α level, antioxidant enzymes (GSH, catalase), lipid peroxidation, and nitrite level in hippocampus and frontal cortex. Triglycerides, total cholesterol, LDL, and HDL levels in serum were also determined. Key Findings. Simvastatin treatment improved cognitive function and locomotor activity in rats. Simvastatin reversed hyperlipidemia and significantly rectified the deleterious effect of AlCl3 on AChE activity. Further, in hippocampus and frontal cortex, aluminium-induced elevation in nitrite and TNF-α and reduction in antioxidant enzymes were inhibited by simvastatin. Conclusion. To conclude, the present study suggests that simvastatin per se protects the neurons in hippocampus and frontal cortex from AlCl3, an environmental toxin. PMID:25802481

  9. Role of the Red Ginseng in Defense against the Environmental Heat Stress in Sprague Dawley Rats.

    Science.gov (United States)

    Kim, Kui-Jin; Yoon, Kye-Yoon; Hong, Hee-Do; Lee, Boo-Yong

    2015-11-10

    Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the effect of RG on heat stress, we examined the effect of the RG on the gene expression profiles in rats subjected to environmental heat stress. We evaluated the transcripts associated with hepatic lipid accumulation and oxidative stress in rats subjected to heat stress. We also analyzed the reactive oxygen species (ROS) contents. Our results suggested RG inhibited heat stress mediated altering mRNA expressions include HSPA1, DEAF1, HMGCR, and FMO1. We also determined RG attenuated fat accumulation in the liver by altering C/EBPβ expression. RG promoted to repress the heat stress mediated hepatic cell death by inhibiting of Bcl-2 expression in rats subjected to heat stress. Moreover, RG administered group during heat stress dramatically decreased the malondialdehyde (MDA) contents and ROS associated genes compared with the control group. Thus, we suggest that RG might influence inhibitory effect on environmental heat stress induced abnormal conditions in humans.

  10. The role of Chinese herbal medicines in a rat model of chronic colitis

    Institute of Scientific and Technical Information of China (English)

    Xiao Lan Tian; Marisabel Mourelle; Yu Ling Li; Francisco Guarner; Juan-R Malagelada

    2000-01-01

    AIM To investigate a mixture of traditional Chinese medicine (TCM) in the prevention of chronic colitis inrats.METHODS Sixty rats were divided into 3 groups. Colitis was induced by trinitrobenzene-sulfonic acid(TNB). On day 10, all the survived rats were killed, the mortality and intestinal obstruction rate werecalculated, the colonic lesion score was assessed and collagenase activity and collagen concentration weremeasured.RESULTS The survival rate was much lower and intestinal obstruction rate much higher in TNB than thosein TCM, they were 53% and 81% vs. 80% and 24% (P<0.05 and P<0.01, respectively). There were alsosignificant differences in colonic stricture score and colonic weight between TNB and TCM groups (1.75±1.2 vs 0.22±0.67 and 0.57±0.36 vs 0.31±0.10, P<0.01 and P<0.05, respectively). No hydroxyprolineand collagenase activity differences were found between the two groups.CONCLUSION This mixture of TCM prevents the formation of intestinal stricture, increases the survivalrate and decreases intestinal obstruction rate in a rat model of chronic colitis.

  11. Amisulpride promotes cognitive flexibility in rats: the role of 5-HT7 receptors.

    Science.gov (United States)

    Nikiforuk, Agnieszka; Popik, Piotr

    2013-07-01

    The antagonism of 5-HT7 receptors may contribute to the antidepressant and procognitive actions of the atypical antipsychotic drug, amisulpride. It has been previously demonstrated that the selective 5-HT7 receptor antagonist reversed restraint stress-induced cognitive impairments in a rat model of frontal-dependent attentional set-shifting task (ASST). Therefore, the first aim of the present study was to assess the effectiveness of amisulpride against stress-evoked cognitive inflexibility. The second goal was to elucidate whether the pro-cognitive effect of amisulpride could be due to the compound's action at 5-HT7 receptors. Rats repeatedly exposed (1 h daily for 7 days) to restraint stress demonstrated impaired performance on the extra-dimensional (ED) set-shifting stage of the ASST. Amisulpride (3 mg/kg) given to stressed rats 30 min before testing reversed this restraint-induced cognitive inflexibility and improved ED performance of the unstressed control group. The 5-HT7 receptor agonist, AS19 (10 mg/kg), abolished the pro-cognitive efficacy of amisulpride (3 mg/kg). The present study suggests that the antagonism of 5-HT7 receptors may contribute to the mechanisms underlining the pro-cognitive action of amisulpride. These results may have therapeutic implications in frontal-like deficits associated with stress-related disorders.

  12. The potential protective role of taurine against 5-fluorouracil-induced nephrotoxicity in adult male rats.

    Science.gov (United States)

    Yousef, Hany N; Aboelwafa, Hanaa R

    2017-02-08

    Nephrotoxicity is common with the use of the chemotherapeutic agent 5-Fluorouracil (5-FU). The current study aimed to investigate the probable protective effect of taurine (TAU) against 5-FU-induced nephrotoxicity in rats using biochemical, histological and ultrastructural approaches. Twenty-four rats were equally divided into control, TAU, 5-FU and 5-FU+TAU groups. 5-FU significantly elevated levels of blood urea nitrogen (BUN), creatinine, and uric acid; while it reduced activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Also, 5-FU induced significant elevation in malondialdehyde (MDA) levels accompanied with marked decline in γ-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) levels in kidney tissues. These biochemical alterations were accompanied by histopathological changes marked by destruction of the normal renal structure, in addition to ultrastructural alterations represented by thickened and irregular glomerular basement membranes, congested glomerular capillaries, damaged lining fenestrated endothelium, mesangial cells hyperplasia with expanded mesangial matrix, and distorted podocyte's processes. Also, the proximal (PCT) and distal (DCT) convoluted tubules showed thickened basement membranes, destructed apical microvilli and loss of basal infoldings of their epithelial cells. Administration of TAU to 5-FU-treated rats reversed most of the biochemical, histological, and ultrastructural alterations. These results indicate that TAU has a protective effect against 5-FU-induced nephrotoxicity.

  13. Seasonal variations of gonadotropins and prolactin in the laboratory rat. Role of maternal pineal gland.

    Science.gov (United States)

    Vázquez, N; Díaz, E; Fernández, C; Jiménez, V; Esquifino, A; Díaz, B

    2007-01-01

    The laboratory rat, a non-photoperiodic rodent, exhibits seasonal fluctuations of melatonin. Melatonin has been found to be readily transferred from the maternal to the fetal circulation. No data exist on the possible influence of maternal pineal gland upon seasonal variations of the offspring. The aim of the present study was to asses the influence of the maternal melatonin rhythm on the offspring postnatal development of the reproductive hormones LH, FSH and prolactin. Male offspring from control, pinealectomized (PIN-X) and PIN-X + melatonin (PIN-X+MEL) mother Wistar rats were studied at 21, 31, and 60 days of age. Seasonal age-dependent variations were found for all hormones studied in control offspring but PIN-X offspring showed a tendency to have reduced duration or altered seasonal variations. Maternal melatonin treatment to PIN-X mothers partially restored the effect of pinealectomy. The chronological study of LH, FSH, and prolactin in PIN-X offspring also showed an altered pattern as compared to control-offspring. Melatonin treatment to the mothers partially restored the developmental pattern of reproductive hormones. Results of this study indicate that maternal pineal gland of the laboratory rat is involved in the seasonal postnatal development variations of reproductive hormones of the offspring.

  14. Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats: role of cannabinoid and vanilloid receptors

    Science.gov (United States)

    Domenicali, M; Ros, J; Fernández-Varo, G; Cejudo-Martín, P; Crespo, M; Morales-Ruiz, M; Briones, A M; Campistol, J-M; Arroyo, V; Vila, E; Rodés, J; Jiménez, W

    2005-01-01

    Background and aims: Anandamide is an endocannabinoid that evokes hypotension by interaction with peripheral cannabinoid CB1 receptors and with the perivascular transient receptor potential vanilloid type 1 protein (TRPV1). As anandamide has been implicated in the vasodilated state in advanced cirrhosis, the study investigated whether the mesenteric bed from cirrhotic rats has an altered and selective vasodilator response to anandamide. Methods: We assessed vascular sensitivity to anandamide, mRNA and protein expression of cannabinoid CB1 receptor and TRPV1 receptor, and the topographical distribution of cannabinoid CB1 receptors in resistance mesenteric arteries of cirrhotic and control rats. Results: Mesenteric vessels of cirrhotic animals displayed greater sensitivity to anandamide than control vessels. This vasodilator response was reverted by CB1 or TRPV1 receptor blockade, but not after endothelium denudation or nitric oxide inhibition. Anandamide had no effect on distal femoral arteries. CB1 and TRPV1 receptor protein was higher in cirrhotic than in control vessels. Neither CB1 mRNA nor protein was detected in femoral arteries. Immunochemistry showed that CB1 receptors were mainly in the adventitia and in the endothelial monolayer, with higher expression observed in vessels of cirrhotic rats than in controls. Conclusions: These results indicate that anandamide is a selective splanchnic vasodilator in cirrhosis which predominantly acts via interaction with two different types of receptors, CB1 and TRPV1 receptors, which are mainly located in perivascular sensory nerve terminals of the mesenteric resistance arteries of these animals. PMID:15753538

  15. Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin and Ficus exasperata

    Directory of Open Access Journals (Sweden)

    Saheed Sabiu

    2015-01-01

    Full Text Available This study investigated the quantitative polyphenolic constituents and gastroprotective effects of aqueous leaf extracts of Spondias mombin and Ficus exasperata against indomethacin-induced gastric ulcer in rats. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg body weight. Wistar rats were pretreated with esomeprazole (reference drug at a dose of 20 mg/kg body weight, S. mombin or F. exasperata at 100 and 200 mg/kg body weight once daily for 21 days prior to ulcer induction. At the end of the experiment, gastric secretions and antioxidant parameters were evaluated. We observed that the significantly increased (p < 0.05 ulcer index, gastric volume, malondialdehyde level and pepsin activity were effectively reduced following treatment with S. mombin and F. exasperata. The extracts also markedly attenuated the reduced activity of superoxide dismutase as well as pH and mucin content in the ulcerated rats. These findings are indicative of gastroprotective and antioxidative potentials of the extracts which is also evident in the degree of % inhibition against ulceration. The available data in this study suggest that the extracts of S. mombin and F. exasperata proved to be capable of ameliorating indomethacin-induced gastric ulceration and the probable mechanisms are via antioxidative and proton pump inhibition.

  16. [Phytoestrogens role in bone functional structure protection in the ovariectomized rat].

    Science.gov (United States)

    Mihalache, Gr; Mihalache, Gr D; Indrei, L L; Indrei, Anca; Hegsted, Maren

    2002-01-01

    Effects of soy protein diet on bone formation and density were evaluated in ovariectomized rats as a model for postmenopausal women. Twenty-seven 9-month-old rats were assigned to 3 treatment groups for the 9-week study: sham-surgery (Sh, n = 9); ovariectomy (Ovx, n = 9); ovariectomy + soy diet (OvxS, n = 9). Rats had free access to an AIN-93 M diet or AIN-93 M diet with 7% soy protein concentration and water. At sacrifice, rear legs were removed, and the right femur and tibia were cleaned manually. Serum alkaline phosphatase, a marker of bone formation, was measured colorimetrically. Bone density was measured using Archimedes' Principle. Alkaline phosphatase activity was greater in OvxS (114 +/- 19 U/L) and Ovx (128 +/- 26 U/L) compared to Sh (110 +/- 22 U/L). Femur bone density was greater for OvxS (1.520 +/- 0.02 g/cc) compared to Ovx (1.510 +/- 0.017 g/cc), but not to Sh (1532 +/- 0.025 g/cc). Tibia bone density was greater for OvxS (1.560 +/- 0.019 g/cc) compared to Ovx (1.553 +/- 0.015 g/cc), but not to Sh (1566 +/- 0.03 g/cc). In conclusion soy protein diet increased the rate of bone formation and bone density in some bones, suggesting that may help prevent bone loss in postmenopausal women.

  17. A Novel Role for the Calcium Sensing Receptor in Rat Diabetic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Shiyun Dong

    2015-01-01

    Full Text Available Background: Diabetic encephalopathy is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations ([Ca2+]i at its onset. The calcium sensing receptor (CaSR is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic encephalopathy remains unclear. Methods: In this study, diabetic rats were modeled by STZ (50 mg/kg. At the end of 4, 8 and 12 weeks, the CaSR expression in hippocampus was analyzed by Western blot. In neonatal rat hippocampal neurons, the [Ca2+]i was detected by laser scanning confocal microscopy, the production of reactive oxygen species (ROS in mitochondria, the level of NO and the mitochondrial transmembrane potential were measured by MitoSOX, DAF-FM and JC-1, respectively. Results: Our results showed in hippocampal neurons treated with high glucose, CaSR regulated [Ca2+]i through the PLC-IP3 pathway. CaSR expression was decreased and was involved in the changes in [Ca2+]i. Mitochondrial membrane potential, NO release and expression of p-eNOS decreased, while the production of ROS in mitochondria increased. Conclusion: Down-regulation of CaSR expression was accompanied by neuronal injury, calcium disturbance, increased ROS production and decreased release of NO. Up-regulation of CaSR expression attenuated these changes through a positive compensatory protective mechanism to inhibit and delay diabetic encephalopathy in rats.

  18. Possible Role of Mast Cells and Neuropeptides in the Recovery Process of Dextran Sulfate Sodium-induced Colitis in Rats

    Institute of Scientific and Technical Information of China (English)

    Ping Zhao; Lei Dong; Jin-yan Luo; Hai-tao Guan; Hui Ma; Xue-qin Wang

    2013-01-01

    Objective To clarify the role of mast cells and neuropeptides substance P (SP),somatostatin (SS),and vasoactive intestinal peptide (VIP) in dextran sulfate sodium (DSS)-induced colitis in rats. Methods Experimental colitis was induced in Sprague-Dawley rats (180-200 g,n=20) by oral in-gestion of 4% (w/v) DSS in drinking water for 7 days. Control rats (n=5) drank water and were sacrificed on day 0. Mast cell number,histamine levels in whole blood and tissue,tissue levels of SP,SS and,VIP in the dis-tal colon of the rats were measured on day 8,day 13,and day 18 of experimentation. Results Oral administration of 4% DSS solution for 7 days resulted in surface epithelial loss and crypt loss in the distal colon. Mast cell count increased on day 8 (1.75±1.09/mm vs. 0.38±0.24/mm,P<0.05) and day 13 (1.55±1.01/mm vs. 0.38±0.24/mm,P<0.05) after DSS treatment. Whole blood his-tamine levels were increased on day 8 (266.93±35.62 ng/mL vs. 76.87±32.28 ng/mL,P<0.01) and gradu-ally decreased by day 13 and day 18 after DSS treatment. Histamine levels in the distal colon were decreased on day 8 (1.77±0.65 ng/mg vs. 3.06±0.87 ng/mg,P<0.05) and recovered to control levels by day 13 after DSS treatment. SP level in the distal colon gradually increased and were raised significantly by day 13 (8777.14±3056.14 pg/mL vs. 4739.66±3299.81 pg/mL,P<0.05) after DSS treatment. SS and VIP levels in the distal colon were not changed. Conclusions Mast cell degranulation followed by histamine release may play an important role in the pathogenesis of colitis induced by DSS. SP may be a significant substance in the progression of inflamma-tion and the recovery process of DSS-induced colitis.

  19. Role of the neuronal histaminergic system in the regulation of somatotropic function: comparison between the neonatal and the adult rat.

    Science.gov (United States)

    Grilli, R; Sibilia, V; Torsello, A; Pagani, F; Guidi, M; Luoni, M; Netti, C; Müller, E E

    1996-11-01

    To study possible age-related differences in the role of neuronal histaminergic pathways in the control of GH secretion, the effects of alpha-fluoromethylhistidine (alpha-FMH), an irreversible inhibitor of histamine (HA) synthesis, were examined on basal and opioid-induced GH release in neonatal and adult rats. The mechanisms involved in such effects were evaluated by measuring pituitary GH mRNA levels and hypothalamic levels of GH-releasing hormone (GHRH) and somatostatin (SRIF) mRNAs. Daily injection of alpha-FMH (20 mg/kg, s.c.) in pups of either sex, from birth until 10 days of age, caused a significant increase in baseline plasma GH and potentiated the GH response to the [Met5]-enkephalin analog FK 33-824 (1 mg/kg, s.c.) administered 3 h after the last alpha-FMH injection. GH and SRIF mRNA levels were significantly higher in alpha-FMH-treated pups than in controls, whereas no difference was observed in GHRH mRNA levels. In young adult male rats, acute administration of alpha-FMH (100 mg/kg, s.c., 3 h before) did not change significantly basal GH levels but potentiated FK 33-824 (0.3 mg/kg, intracarotid)-induced stimulation of GH secretion. Repeated administration of alpha-FMH (200 micrograms/rat, i.c.v., for 3 days) failed to modify basal and FK 33-824-induced GH secretion, caused a significant reduction in hypothalamic GHRH mRNA levels and left SRIF and GH mRNAs unchanged. These findings indicate that HA exerts an inhibitory effect on GH secretion in both neonatal and adult rats. The different effects of short-term HA depletion on hypothalamic and pituitary indices of somatotropic function observed at the two age periods may be ascribed to the immaturity of the HA system in early postnatal life and to a different functional role of GH-regulatory factors during ontogeny.

  20. Protective role of mitochondrial K-ATP channel and mitochondrial membrane transport pore in rat kidney ischemic postconditioning

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei-liang; ZHAO Yan-li; LIU Xiao-ming; CHEN Jing; ZHANG Dong

    2011-01-01

    Background Previous studies suggested that mechanical intervention during early reperfusion, or ischemia postconditioning (Ipo), could protect kidneys against renal ischemia reperfusion injury (RIRI). However, the mechanisms responsible for this protection remain unclear. This study therefore investigated the protection afforded by Ipo in rat kidneys in vivo, and the roles of mitochondrial KATP channels (mitOKATP) and mitochondrial permeability transition pores (MPTPs), by inhibiting mitOKATP with 5-hydroxydecanoate (5-HD), and by directly detecting open MPTPs using calcein-AM and CoCl2.Methods Thirty-five male Sprague-Dawley rats were randomly assigned to sham-operation (S), ischemia-reperfusion (I/R),Ipo, ischemia reperfusion with 5-HD (I/R+5-HD), or Ipo with 5-HD (Ipo +5-HD) groups. Rats in each group were sacrificed after 6 hours of reperfusion by heart exsanguination or cervical dislocation under anesthesia. RIRI was assessed by determination of creatinine and blood urea nitrogen (BUN), and by examination of histologic sections. The roles of mitoKATP and MPTP were investigated by analyzing fluorescence intensities of mitochondria, mitochondrial membrane potential,intracellular reactive oxygen species (ROS) and intracellular calcium, using appropriate fluorescent markers. The relationship between apoptosis and RIRI was assessed by determining the apoptotic index (Al) of kidney tubular epithelial cells.Results The RIRI model was shown to be successful. Significantly higher levels of creatinine and BUN, and abnormal pathology of histologic sections, were observed in group I/R, compared with group S. 5-HD eliminated the renoprotective effects of Ipo. Mitochondrial and mitochondrial membrane potential fluorescence intensities increased, and intracellular calcium, ROS fluorescence intensities and AI decreased in group Ipo, compared with group I/R. However, mitochondrial and mitochondrial membrane potential fluorescence intensities decreased, and intracellular

  1. Role of Nitric Oxide in Shiga Toxin-2-Induced Premature Delivery of Dead Fetuses in Rats

    Science.gov (United States)

    Burdet, Juliana; Zotta, Elsa; Cella, Maximiliano; Franchi, Ana M.; Ibarra, Cristina

    2010-01-01

    Shiga toxin-producing Escherichia coli (STEC) infections could be one of the causes of fetal morbimortality in pregnant women. The main virulence factors of STEC are Shiga toxin type 1 and/or 2 (Stx1, Stx2). We previously reported that intraperitoneal (i.p.) injection of rats in the late stage of pregnancy with culture supernatant from recombinant E. coli expressing Stx2 and containing lipopolysaccharide (LPS) induces premature delivery of dead fetuses. It has been reported that LPS may combine with Stx2 to facilitate vascular injury, which may in turn lead to an overproduction of nitric oxide (NO). The aim of this study was to evaluate whether NO is involved in the effects of Stx2 on pregnancy. Pregnant rats were i.p. injected with culture supernatant from recombinant E. coli containing Stx2 and LPS (sStx2) on day 15 of gestation. In addition, some rats were injected with aminoguanidine (AG), an inducible isoform inhibitor of NO synthase (iNOS), 24 h before and 4 h after sStx2 injection. NO production was measured by NOS activity and iNOS expression by Western blot analysis. A significant increase in NO production and a high iNOS expression was observed in placental tissues from rats injected with sStx2 containing 0.7 ng and 2 ng Stx2/g body weight and killed 12 h after injection. AG caused a significant reduction of sStx2 effects on the feto-maternal unit, but did not prevent premature delivery. Placental tissues from rats treated with AG and sStx2 presented normal histology that was indistinguishable from the controls. Our results reveal that Stx2-induced placental damage and fetus mortality is mediated by an increase in NO production and that AG is able to completely reverse the Stx2 damages in placental tissues, but not to prevent premature delivery, thus suggesting other mechanisms not yet determined could be involved. PMID:21206910

  2. Role of gap junctions in acetylcholine-induced vasodilation of proximal and distal arteries of the rat mesentery.

    Science.gov (United States)

    Hill, C E; Hickey, H; Sandow, S L

    2000-07-01

    We have previously shown that myoendothelial gap junctions are more prevalent in distal than in proximal arteries of the rat mesentery. In the present study we have investigated the role of gap junctions in the mechanism of action of endothelium-derived hyperpolarizing factor (EDHF) in these same vessels following relaxation with acetylcholine. Arteries were pre-constricted with phenylephrine and concentration response curves to acetylcholine were constructed in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) and indomethacin (10(-5) M) to prevent effects due to the release of nitric oxide and prostacyclins. Nitric oxide was found to have only a small role in the relaxation of the proximal vessels and was not involved in the relaxations of the distal vessels. 18 alpha-Glycyrrhetinic acid (10(-5) M), a putative gap junction uncoupler, significantly reduced acetylcholine-induced relaxations by 50% in both proximal and distal vessels. Potassium channel antagonists, tetraethylammonium chloride (TEA; 10(-3) M) and barium chloride (10(-4) M), together abolished the dilatory response in the proximal mesenteric arteries, but did not completely block responses in the distal arteries. The data suggest that gap junctions contribute significantly to the acetylcholine-induced relaxation in both proximal and distal arteries of the rat mesentery. We hypothesize that the absence of a correlation between the role of gap junctions and the incidence of myoendothelial gap junctions in these same vessels is due to significant effects of the inhibitors on gap junctions located in the smooth muscle layers of the larger vessels.

  3. A critical role for the melanocortin 4 receptor in stress-induced relapse to nicotine seeking in rats.

    Science.gov (United States)

    Qi, Xiaoli; Yamada, Hidetaka; Corrie, Lu W; Ji, Yue; Bauzo, Rayna M; Alexander, Jon C; Bruijnzeel, Adrie W

    2015-03-01

    Tobacco addiction is characterized by a lack of control over smoking and relapse after periods of abstinence. Smoking cessation leads to a dysphoric state that contributes to relapse to smoking. After the acute withdrawal phase, exposure to stressors increases the risk for relapse. Blockade of melanocortin 4 (MC4 ) receptors has anxiolytic and antidepressant-like effects in animal models. The aim of these studies was to investigate the role of MC4 receptors in the dysphoria associated with nicotine withdrawal and stress-induced reinstatement of nicotine seeking. To study stress-induced reinstatement, rats self-administered nicotine for 16 days and then nicotine seeking was extinguished by substituting saline for nicotine. Nicotine seeking was reinstated by intermittent footshock stress. The intracranial self-stimulation (ICSS) procedure was used to assess the negative mood state associated with nicotine withdrawal. Elevations in the ICSS thresholds are indicative of a dysphoric state. The selective MC4 receptor antagonists HS014 and HS024 prevented stress-induced reinstatement of extinguished nicotine seeking. Drug doses that prevented stress-induced relapse did not affect responding for food pellets, which indicates that the drugs did not induce sedation or motor impairments. In the ICSS experiments, the nicotinic acetylcholine receptor antagonist mecamylamine elevated the ICSS thresholds of the nicotine-dependent rats. Pre-treatment with HS014 or HS024 did not prevent the elevations in ICSS thresholds. These studies indicate that MC4 receptors play a critical role in stress-induced reinstatement of nicotine seeking, but these receptors may not play a role in the dysphoria associated with acute nicotine withdrawal.

  4. Role of PKCδ in Enhanced Expression of Gqα/PLCβ1 Proteins and VSMC Hypertrophy in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Atef, Mohammed Emehdi; Anand-Srivastava, Madhu B

    2016-01-01

    Gqα signaling has been implicated in cardiac hypertrophy. In addition, angiotensin II (Ang II) was also shown to induce its hypertrophic effect through Gqα and PKCδ activation. We recently showed the role of enhanced expression of Gqα/PLCβ1 proteins in vascular smooth muscle cell (VSMC) hypertrophy, however, the role of PKCδ in VSMC hypertrophy in animal model is still lacking. The present study was therefore undertaken to examine the role of PKCδ and the associated signaling mechanisms in VSMC hypertrophy using 16-week-old spontaneously hypertensive rats (SHR). VSMC from 16-week-old SHR exhibited enhanced phosphorylation of PKCδ-Tyr311 and increased protein synthesis, marker of hypertrophy, as compared to WKY rats which was attenuated by rottlerin, an inhibitor of PKCδ. In addition, knocking down of PKCδ by PKCδ-siRNA also attenuated enhanced protein synthesis in VSMC from SHR. Furthermore, rottlerin attenuated the increased production of superoxide anion, NAD(P)H oxidase activity, increased expression of Gqα, phospholipase C (PLC)β1, insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) proteins in VSMC from SHR. In addition, the enhanced phosphorylation of c-Src, PKCδ-Tyr311, IGF-1R, EGFR and ERK1/2 exhibited by VSMC from SHR was also attenuated by rottlerin. These results suggest that VSMC from SHR exhibit enhanced activity of PKCδ and that PKCδ is the upstream molecule of reactive oxygen species (ROS) and contributes to the enhanced expression of Gqα and PLCβ1 proteins and resultant VSMC hypertrophy involving c-Src, growth factor receptor transactivation and MAP kinase signaling.

  5. Roles of HDAC2 and HDAC8 in Cardiac Remodeling in Renovascular Hypertensive Rats and the Effects of Valproic Acid Sodium.

    Science.gov (United States)

    Li, Rui-Fang; Cao, Shan-Shan; Fang, Wei-Jin; Song, Ying; Luo, Xue-Ting; Wang, Hong-Yun; Wang, Jian-Gang

    2017-01-01

    Recent studies indicate that histone deacetylases (HDACs) activity is associated with the development and progression of cardiac hypertrophy. In this study, we investigated the effects of a HDACs inhibitor, valproic acid sodium (VPA), on cardiac remodeling and the differential expression of HDACs in left ventricles (LVs) of renovascular hypertensive rats. Renovascular hypertension was induced in rats by the two-kidney two-clip (2K2C) method. Cardiac remodeling, heart function and the differential expression of HDACs were examined at different weeks after 2K2C operation. The effects of VPA on cardiac remodeling, the expressions of HDACs, transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF) in LV were investigated. The expressions of atrial natriuretic factor, β-myosin heavy chain, HDAC2 and HDAC8 increased in LV of 2K2C rats at 4, 8, 12 weeks after operation. Cardiac dysfunction, cardiac hypertrophy and fibrosis were markedly attenuated by VPA treatment in 2K2C rats. Further studies revealed that VPA inhibited the expressions of HDAC2, HDAC8, TGF-β1 and CTGF in LV of 2K2C rats. In summary, these data indicate that HDAC2 and HDAC8 play a key role in cardiac remodeling in renovascular hypertensive rats and that VPA attenuates hypertension and cardiac remodeling. The effect of VPA is possibly exerted via decreasing HDAC2, HDAC8, TGF-β1 and CTGF expressions in LV of 2K2C rats.

  6. Differential role of P-glycoprotein and breast cancer resistance protein in drug distribution into brain, CSF and peripheral nerve tissues in rats.

    Science.gov (United States)

    Huang, Liyue; Li, Xingwen; Roberts, Jonathan; Janosky, Brett; Lin, Min-Hwa Jasmine

    2015-01-01

    1. This study was designed to evaluate how the absence of P-glycoprotein (Pgp, Mdr1a), breast cancer-resistance protein (Bcrp, Abcg2) or both affects drug distribution into sciatic nerves, brain and cerebrospinal fluid (CSF) in rats. 2. Pgp substrate (loperamide), BCRP substrates (dantrolene and proprietary compound X) and dual substrates (imatinib and proprietary compound Y) were well distributed into sciatic nerves with comparable nerve to plasma concentration ratios between wild-type and knockout (KO) rats. 3. Brain exposure increased substantially in Mdr1a(-/-) rats for loperamide and in Mdr1a(-/-)/Abcg2(-/-) rats for imatinib and compound Y, but minimally to modestly in Abcg2(-/-) rats for dantrolene and compound X. The deletion of Mdr1a or Abcg2 alone had little effect on brain distribution of compound Y. 4. While CSF to unbound brain concentration ratio remained ≥3 in the KO animals for dantrolene, compounds X and Y, it was reduced to 1 in the Mdr1a(-/-)/Abcg2(-/-) rats for imatinib. 5. The data indicate that Pgp and Bcrp do not play significant roles in drug distribution into peripheral nerve tissues in rats, while working in concert to regulate brain penetration. Our results further support that CSF concentration may not be a good surrogate for unbound brain concentration of efflux substrates.

  7. Uncertainty, Conventions and Co-ordination in the Business Enterprise

    DEFF Research Database (Denmark)

    Jagd, Søren

    The paper presents the basic propositions of convention theory with special consideration to the analysis of uncertainty, the role of institutions and conventions, and the implications this perspective has for the analysis of the business enterprise......The paper presents the basic propositions of convention theory with special consideration to the analysis of uncertainty, the role of institutions and conventions, and the implications this perspective has for the analysis of the business enterprise...

  8. The Role of Nerve Growth Factor in Ginsenoside Rg1-Induced Regeneration of Injured Rat Sciatic Nerve.

    Science.gov (United States)

    Huo, Dong-Sheng; Zhang, Ming; Cai, Zhi-Ping; Dong, Chao-Xuan; Wang, He; Yang, Zhan-Jun

    2015-01-01

    Sciatic nerve injury is commonly seen in clinical practice predominantly associated with trauma or sports injuries. Recent studies indicated that ginsenoside Rg1 (Gs Rg1), extracted from Chinese herbs, was found to promote regeneration of injured rat sciatic nerve and that nerve growth factor (NGF) may be involved in this process. The aim of this study was to examine the role that NGF may play in ginsenoside Rg1-induced regeneration of rat sciatic nerve following injury. Animals following surgical right sciatic nerve injury were subsequently administered intraperitoneally either saline (sham control) or different doses of 2, 4, 8, or 12 mg/kg daily GsRg1 for 2 to 8 wk. In addition, 100 μg/kg mecobalamin, a drug utilized to treat nerve injuries, was employed as a positive control. After 2, 4, or 8 wk, sciatic functional index (SFI) and mean nerve conduction velocity (MNCV), markers of sciatic nerve function, were assessed to determine whether recovery of injured sciatic nerve occurred. In addition, immunohistochemistry and Western blot methods were used to examine NGF protein expression changes. Results showed that all doses of GsRg1 significantly increased SFI and MNCV in injured sciatic-nerve-damaged rats in a manner similar to that noted with mecobalamin. It is of interest that the intermediate 4- and 8-mg/kg doses were more effective in restoring nerve functions. Immunohistochemistry and Western blot results also demonstrated a similar pattern with enhanced NGF protein expression at all doses, but greater effects were noted at 4 and 8 mg/kg GsRg1. Data suggest that GsRg1 promotes recovery of injured sciatic nerve functions within a specific dose range and that NGF may be involved in this physiological process.

  9. Role of Protective Effect of L-Carnitine against Acute Acetaminophen Induced Hepatic Toxicity in Adult Albino Rats

    Directory of Open Access Journals (Sweden)

    Zeinab M. Gebaly* and Gamal M. Aboul Hassan

    2012-10-01

    Full Text Available Background: Acetaminophen, a widely used analgesic and antipyretic is known to cause hepatic injury in humans and experimental animals when administered in high doses. It was reported that toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing to the beta-oxidation of fatty acid in the mitochondria. It is a known antioxidant with protective effects against lipid peroxidation. This study aimed to investigate the possible beneficial effect of L-carnitine as an antioxidant agent against acetaminophen induced hepatic toxicity in rats. Material and Methods: Four rat groups (N=7 in each group. Group I is the control, group II received 500 mg/kg/ body weight of L-carnitine for 7 days by oral route, group III received 640/kg/ bw of acetaminophen by oral route, group IV acute acetaminophen group pretreated with L-carnitine for 7 days by gastric tube gavage tube. The liver of all rats were removed for investigation using light and electro microscopic studies. Results: Acetaminophen caused massive centrilobular necrosis and massive degenerative changes. The electron-microscopic study showed few mitochondria, increased fat droplets and scanty smooth endoplasmic reticulum (SER, rough endoplasmic reticulum (RER.These changes were reduced by L-carnitine pretreatment. Conclusion: those results suggest that acetaminophen results damage in the liver as an acute effect and L-carnitine ameliorated the adverse effects of acetaminophen via its antioxidant role

  10. Role of dopamine and GABA in the control of motor activity elicited from the rat nucleus accumbens.

    Science.gov (United States)

    Wong, L S; Eshel, G; Dreher, J; Ong, J; Jackson, D M

    1991-04-01

    The application of 1.2 and 12.0 micrograms/side of the GABAA receptor agonist 3-aminopropane sulphonic acid bilaterally into the nucleus accumbens (Acb) of rats nonsignificantly depressed locomotor activity as assessed in automated Animex activity cages, while the highest dose (60 micrograms/side) significantly stimulated activity. The GABAA receptor antagonists picrotoxinin (0.0625 and 0.125 micrograms/saide) and bicuculline (0.895 micrograms/side) produced forward locomotion around the cage accompanied by a number of other behaviours. The GABAB agonist baclofen (0.023 and 0.092 micrograms/side) induced a short-lasting (18 min) locomotor depression. None of the GABAB antagonists tested (2-hydroxysaclofen 2.6 micrograms/side, two novel beta-(benzo[b]furan) analogues of baclofen 9G or 9H each 6.8 micrograms/side, 4-aminobutylphosphonic acid 1.32 micrograms/side and phaclofen 0.535 and 2 micrograms/side) significantly affected locomotor activity. In rats pretreated with reserpine and alpha-methyl-p-tyrosine, picrotoxinin (0.0625 and 0.125 micrograms/side) did not significantly alter locomotor activity. Furthermore, when picrotoxinin (0.0625 micrograms/side) was combined with either the selective dopamine (DA) D1 agonist SKF38393 or the selective D2 agonist quinpirole, no significant alteration in locomotor function occurred. When SKF38393 and quinpirole were coadministered, significant stimulation occurred which was further enhanced by the addition of picrotoxinin. It is concluded that GABAA receptors, together with D1 and D2 receptors, play a major role in modulating the control of motor function by the Acb of rats.

  11. Methotrexate-induced nitrosative stress may play a critical role in small intestinal damage in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Kolli, Viswa Kalyan; Abraham, Premila [Christian Medical College, Department of Biochemistry, Vellore, Tamil Nadu (India); Rabi, Suganthy [Christian Medical College, Department of Anatomy, Vellore, Tamil Nadu (India)

    2008-10-15

    Methotrexate (MTX), a structural analogue of folic acid, is widely used as a chemotherapeutic agent for leukemia and other malignancies. One of the major toxic effects of MTX is intestinal injury and enterocolitis.The mechanism of gastrointestinal toxicity of methotrexate has not been investigated completely. Therefore cancer chemotherapy has to be accompanied by symptomatic therapy such as antibiotics and anti-diarrheal drugs. It is important to investigate the mechanism by which methotrexate induces intestinal damage in order to perform cancer chemotherapy effectively by preventing the side effects. This study aimed at investigating whether nitrosative stress plays a role in methotrexate induced small intestinal damage using a rat model. Adult male rats were administered methotrexate at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the final dose of methotrexate. Vehicle treated rats served as control. The intestinal tissue was used for light microscopic studies and markers of nitrosative stress including tissue nitrite level and nitrotyrosine. Myeloperoxidase (MPO) activity, a marker of neutrophil infiltration was also measured in intestinal homogenates. The villi were damaged at 12 h and the damage progressed and became severe at 24 h after the final dose of MTX. Biochemically, tissue nitrate was elevated fivefold at 12 h and fourfold at 24 h after the final dose of MTX as compared with control. Nitrotyrosine, measured immunohistochemically was detected in all the parts of the small intestine. Duodenum stained the most for nitrotyrosine, followed by ileum and then jejunum. The staining for nitrotyrosine was more intense at 24 h as compared with 12 h after the final dose of methotrexate. There was marked neutrophil infiltration as evidenced by increase in MPO activity in the small intestines. In conclusion, the results of the present study reveal that nitrosative stress may play a critical role in

  12. Role of peroxisome proliferator-activated receptor a activation in acute myocardial damage induced by isoproterenol in rats

    Institute of Scientific and Technical Information of China (English)

    YUAN Jie; WU Jian; HANG Zhi-gang; ZHONG Xue-kuan; ZHOU Ling-wang; YU Bo

    2008-01-01

    Background Peroxisome proliferator-activated receptor(PPAR)a is one of the subtypes of PPARs.It regulates metabolism of lipid and lipoprotein,as well as glucose homeostasis.In addition,PPARa influences cellular proliferation, inflammation,differentiation and apoptosis,which plays a vital role in cardiovascular diseases.The purpose of this study was to investigate the role and mechanisms of PPARa activation in relation to acute myocardial damage induced by isoproterenol in rats.Methods Thirty male Wister rats were randomly divided into controI group,isoproterenol (Iso)injured group and fenofibrate(FF)treatment group.Acute myocardiaI damage caused by isoproterenol intraperitoneaI injection induced ischemia was established.We determined the levels of creatine kinase(CK)and lactic dehvdroqenase(LDH)in serum as welI as the concentrations of free fatty acids(FFA)in serum and myocardium.The mRNA expressions of PPARa, muscular type carnitine palmitransferase(M-CPT-1)and medium chain lipid acetyl coenzyme A dehydrogenase(MCAD) were analyzed by reverse transcription-polymerase chain reaction(RT-PCR).Results Compared with the control group.the Ievels of serum CK and LDH were significantly increased after FF and ISO treatments.Moreover.the concentrations of FFA in both serum and myocardium were obviously increased in the ISO group and FF group,while the mRNA expressions of PPARa,M-CPT-I and MCAD declined,respectively(P≤0.01).When compared with the lSO group.significant decreases in serum CK and LDH were obsewed in the FF group.The concentrations of FFA both in serum and myocardiaI tissue were markedly decreased in the FF group.while the expressions of PPARo.M-CPT-I and MCAD mRNA were increased(vs Iso,P≤O.01).Conclusions The utilization of FFA was reduced in isoproterenol induced acute myocardial damage.PPARa activation by its activator fenofibrate may play a key role in energy metabolism in acute myocardial damage induced by isoproterenol in rats.

  13. Rolipram Attenuates Bile Duct Ligation–Induced Liver Injury in Rats: A Potential Pathogenic Role of PDE4

    Science.gov (United States)

    Barve, Shirish; Breitkopf-Heinlein, Katja; Li, Yan; Zhang, JingWen; Avila, Diana V.; Dooley, Steven; McClain, Craig J.

    2013-01-01

    Anti-inflammatory and antifibrotic effects of the broad spectrum phosphodiesterase (PDE) inhibitor pentoxifylline have suggested an important role for cyclic nucleotides in the pathogenesis of hepatic fibrosis; however, studies examining the role of specific PDEs are lacking. Endotoxemia and Toll-like receptor 4 (TLR4)-mediated inflammatory and profibrotic signaling play a major role in the development of hepatic fibrosis. Because cAMP-specific PDE4 critically regulates lipopolysaccharide (LPS)-TLR4–induced inflammatory cytokine expression, its pathogenic role in bile duct ligation-induced hepatic injury and fibrogenesis in Sprague-Dawley rats was examined. Initiation of cholestatic liver injury and fibrosis was accompanied by a significant induction of PDE4A, B, and D expression and activity. Treatment with the PDE4-specific inhibitor rolipram significantly decreased liver PDE4 activity, hepatic inflammatory and profibrotic cytokine expression, injury, and fibrosis. At the cellular level, in relevance to endotoxemia and inflammatory cytokine production, PDE4B was observed to play a major regulatory role in the LPS-inducible tumor necrosis factor (TNF) production by isolated Kupffer cells. Moreover, PDE4 expression was also involved in the in vitro activation and transdifferentiation of isolated hepatic stellate cells (HSCs). Particularly, PDE4A, B, and D upregulation preceded induction of the HSC activation marker α-smooth muscle actin (α-SMA). In vitro treatment of HSCs with rolipram effectively attenuated α-SMA, collagen expression, and accompanying morphologic changes. Overall, these data strongly suggest that upregulation of PDE4 expression during cholestatic liver injury plays a potential pathogenic role in the development of inflammation, injury, and fibrosis. PMID:23887098

  14. The Protective Role of Mecobalamin Following Optic Nerve Crush in Adult Rats

    Institute of Scientific and Technical Information of China (English)

    Xiangmei Kong; Xinghuai Sun; Jinjun Zhang

    2004-01-01

    Purpose: To evaluate the potential for Mecobalamin as a neuroprotective agent in optic nerve crush injury.Methods: Twenty-four adult Sprague-Dawley rats were randomly divided into four groups.One group acted as normal controls, while in the other three groups the right eye was subjected to optic nerve crush injury. Of the three crush injury groups one group received no treatment, while the other two groups received intramuscular injections of VitaminB12 or Mecobalamin (10μg) immediately after crush injury and then every two days. All the rats were sacrificed one month post-treatment, and the eyes attached with optic nerves were removed for histology. The morphological changes of optic nerve axons and retinal ganglion cells (RGCs) were assessed under light microscope (LM) and transmission electromicroscope (TEM). The numbers of axons and RGCs were counted.Results: In this study we demonstrate the potential for Mecobalamin as a neuroprotective agent following optic nerve crush injury. We show here that the axons of optic nerves were loose in structure or destroyed. The mitochondria of the RGCs was swollen, and the Nissel body was less evident after the crush injury. Moreover, the number of axons and RGCs was significantly reduced (P < 0.001). However, these changes were less dramatic after the Mecobalamin-treatment. More axons and RGCs were remained in the group than those in the untreated injury group (P = 0.010 and 0.003 respectively), and those in the VitaminB12-treated group (P=0.037 and 0.035 respectively). More significantly, there were newly formed axons found in the Mecobalamin-treated group.Conclusions: Optic nerve crush injury in rats causes the loss of the axons and RGCs but this may be ameliorated by treatment with Mecobalamin.

  15. The protective role of saffron petal extracts on gentamicininduced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Arash Omidi

    2016-07-01

    Full Text Available Different potentially therapeutic approaches to prevent or attenuate gentamicin sulfate (GM induced nephrotoxicity have been proposed. The present study was conducted to investigate the effect of the saffron petals extracts (Crocus sativus (SPE on male Wistar rats with kidney failure. Rats (40 were randomly assigned into five groups of 8 animals each: i the control group, that received normal saline (0.5 mL/kg; ii the GM group, that received GM (80 mg/kg by intraperitoneal (i.p. injection on a daily basis; iii the GM+SPE group that received the same dose of GM and SPE (40 mg/kg by i.p. injection on a daily basis; iv the GM+2SPE group, that received the same dose of GM and twofold of SPE (80 mg/kg by i.p. injection on a daily basis; whereas v 2SPE+GM group, that received 80 mg/kg of SPE a week before initiating the treatment with GM (prevention group. Significant differences were seen in the concentration of glucose, blood urea nitrogen (BUN, and creatinine between treatment groups and control in the male Wistar rats. GM was observed to cause nephrotoxicity, which was evidenced by an elevation of serum BUN and creatinine levels. The biochemical findings of the current study are concordant with those of histopathologic findings. The results of this study indicate that SPE especially in dose of 40 mg/kg can ameliorate harmful effects of GM on the kidney. The present results may suggest that the SPE have ameliorative effects on kidney failures induced by GM.

  16. Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors

    Science.gov (United States)

    Blaha, Igor; Recio, Paz; Martínez, María Pilar; López-Oliva, María Elvira; Ribeiro, Ana S. F.; Agis-Torres, Ángel; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Fernandes, Vítor S.; Hernández, Medardo

    2016-01-01

    Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR. PMID:27285468

  17. Dissociable roles of dopamine and serotonin transporter function in a rat model of negative urgency.

    Science.gov (United States)

    Yates, Justin R; Darna, Mahesh; Gipson, Cassandra D; Dwoskin, Linda P; Bardo, Michael T

    2015-09-15

    Negative urgency is a facet of impulsivity that reflects mood-based rash action and is associated with various maladaptive behaviors in humans. However, the underlying neural mechanisms of negative urgency are not fully understood. Several brain regions within the mesocorticolimbic pathway, as well as the neurotransmitters dopamine (DA) and serotonin (5-HT), have been implicated in impulsivity. Extracellular DA and 5-HT concentrations are regulated by DA transporters (DAT) and 5-HT transporters (SERT); thus, these transporters may be important molecular mechanisms underlying individual differences in negative urgency. The current study employed a reward omission task to model negative urgency in rats. During reward trials, a cue light signaled the non-contingent delivery of one sucrose pellet; immediately following the non-contingent reward, rats responded on a lever to earn sucrose pellets (operant phase). Omission trials were similar to reward trials, except that non-contingent sucrose was omitted following the cue light prior to the operant phase. As expected, contingent responding was higher following omission of expected reward than following delivery of expected reward, thus reflecting negative urgency. Upon completion of behavioral training, Vmax and Km were obtained from kinetic analysis of [(3)H]DA and [(3)H]5-HT uptake using synaptosomes prepared from nucleus accumbens (NAc), dorsal striatum (Str), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC) isolated from individual rats. Vmax for DAT in NAc and for SERT in OFC were positively correlated with negative urgency scores. The current findings suggest that mood-based impulsivity (negative urgency) is associated with enhanced DAT function in NAc and SERT function in OFC. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Use of antiserum to neurotensin reveals a physiological role for the peptide in rat prolactin release.

    Science.gov (United States)

    Vijayan, E; Carraway, R; Leeman, S E; McCann, S M

    1988-01-01

    Previous studies have indicated that the brain peptide neurotensin can stimulate prolactin release by direct action on the pituitary gland, whereas its action within the hypothalamus is inhibitory. The inhibitory action is mediated by the release of dopamine into the hypophyseal portal veins, which deliver the neurotransmitter to the anterior pituitary gland to inhibit prolactin release. Our experiments were done to evaluate the physiologic significance of these neurotensin actions by injecting the globulin fraction of highly specific neurotensin antiserum either intravenously or intraventricularly. Injection into the third ventricle of either 1 or 3 microliter of neurotensin antiserum significantly increased plasma prolactin concentrations in (i) ovariectomized and (ii) ovariectomized estrogen- and progesterone-primed rats within 1 hr of injection. The response was more pronounced in the ovariectomized than in the ovariectomized estrogen- and progesterone-treated animals and was dose related. Intraventricular injection of these doses of neurotensin antiserum also evoked elevations in plasma prolactin in intact males, which were significant but smaller in magnitude than those seen in female rats. To evaluate the effect of the antiserum on the pituitary directly, the antiserum was injected intravenously at a dose of 40 microliter, which was sufficient to block the blood pressure-lowering effect of neurotensin. After the intravenous injection of antiserum, a highly significant suppression of plasma prolactin occurred, detectable when first measured at 1 hr after injection in both ovariectomized and ovariectomized estrogen- and progesterone-treated animals; however, the intravenous injection of antiserum had no significant effect on the prolactin release in males. These data indicate the physiological significance of the hypothalamic inhibitory actions of neurotensin on prolactin release, which are probably mediated by its stimulation of dopamine release that in turn

  19. Endometriosis-induced vaginal hyperalgesia in the rat: role of the ectopic growths and their innervation.

    Science.gov (United States)

    McAllister, Stacy L; McGinty, Kristina A; Resuehr, David; Berkley, Karen J

    2009-12-15

    Endometriosis is a painful disorder defined by extrauteral endometrial growths whose contribution to pain symptoms is poorly understood. Endometriosis is created in rats by autotransplanting on abdominal arteries pieces of either uterus (ENDO), which form cysts, or fat (shamENDO), which do not form cysts. ENDO, but not shamENDO induces vaginal hyperalgesia. We tested the hypothesis that the cysts are necessary to maintain vaginal hyperalgesia by assessing the effect of surgically removing them. Complete-cyst-removal eliminated ENDO-induced vaginal hyperalgesia up to 4 months post-operatively. Sham-cyst-removal in ENDO rats, in which cysts were not removed, or partial cyst-removal increased the ENDO-induced hyperalgesia. The decreases and increases both took 3-6 weeks to develop. Changes in ENDO-induced hyperalgesia did not occur in a control group of ENDO rats who had no surgery after ENDO. In a double-surgery control group, neither shamENDO surgery nor a subsequent sham surgery that mimicked "removal" of non-existent cysts influenced vaginal nociception. In a no-surgery control group, vaginal nociception remained stable for >6 months. The increases in ENDO-induced hyperalgesia produced by the sham-cyst-removal surgery were smaller in proestrus than in other estrous stages. During the other stages (but not during proestrus), sympathetic innervation of the cysts increased. These results suggest that maintenance of ENDO-induced vaginal hyperalgesia requires continued presence of at least some ectopic endometrial tissue, and that surgical treatment that fails to remove ectopic endometrial tissue can exacerbate the hyperalgesia, possibly due in part to an increase in the cysts' sympathetic innervation.

  20. The role of nitric oxide in saline-induced natriuresis and diuresis in rats.

    Science.gov (United States)

    Noonan, W T; Banks, R O

    1999-09-01

    This study was designed to determine to what extent nitric oxide (NO) mediates the natriuretic and diuretic responses to acute isotonic saline (0.9 gram % NaCl) volume expansion (SVE, 0.5 ml min-1 kg-1). Studies were performed on 49 pentobarbital anesthetized (65 mg/kg) female Sprague-Dawley rats with or without a NO synthase inhibitor, Nomega-nitro-L-arginine (LNA). Group 1 received saline at 27 microliter/min for 1 hr (baseline) and then SVE for 1 hr; Groups 2-4 received LNA at 10, 150, and 200 microgram kg-1 min-1, respectively, for 1 hr followed by LNA + SVE. To determine to what extent inhibition of NOS would reverse an ongoing SVE-induced natriuresis and diuresis, Group 5 was saline-volume-expanded for hours 1 and 2 whereas Group 6 was administered SVE during the first hour and then SVE + 150 microgram kg -1 min-1 LNA during the second hour. SVE caused a significant (P natriuresis or diuresis in these animals). Along these lines, there was a small but significant positive linear correlation coefficient (r = 0.41, P = 0.05) between sodium excretion values and corresponding MAP values in SVE control rats but not in Groups 3-4 during SVE (r = 0.28, P = 0.26). The current data demonstrate that 1) NO does not mediate SVE-induced hyperfiltration in the rat, 2) NO also does not mediate SVE-induced natriuresis or diuresis, and 3), consistent with other reports, NO appears to mediate pressure natriuresis and diuresis.

  1. Androgenic effect of honeybee drone milk in castrated rats: roles of methyl palmitate and methyl oleate.

    Science.gov (United States)

    Seres, A B; Ducza, E; Báthori, M; Hunyadi, A; Béni, Z; Dékány, M; Hajagos-Tóth, J; Verli, J; Gáspár, Róbert

    2014-04-28

    Numerous honeybee (Apis mellifera) products have been used in traditional medicine to treat infertility and to increase vitality in both men and women. Drone milk (DM) is a relatively little-known honeybee product with a putative sexual hormone effect. The oestrogenic effect of a fraction of DM has recently been reported in rats. However, no information is available on the androgenic effects of DM. The purpose of the present study was to determine the androgen-like effect of DM in male rats and to identify effective compounds. A modified Hershberger assay was used to investigate the androgenic effect of crude DM, and the plasma level of testosterone was measured. The prostatic mRNA and protein expression of Spot14-like androgen-inducible protein (SLAP) were also examined with real-time PCR and Western blot techniques. GC-MS and NMR spectroscopic investigations were performed to identify the active components gained by bioactivity-guided fractionation. The crude DM increased the relative weights of the androgen-dependent organs and the plasma testosterone level in castrated rats and these actions were flutamide-sensitive. DM increased the tissue mRNA and protein level of SLAP, providing further evidence of its androgen-like character. After bioactivity-guided fractionation, two fatty acid esters, methyl palmitate (MP) and methyl oleate (MO), were identified as active compounds. MP alone showed an androgenic effect, whereas MO increased the weight of androgen-sensitive tissues and the plasma testosterone level only in combination. The experimental data of DM and its active compounds (MO and MP) show androgenic activity confirming the traditional usage of DM. DM or MP or/and MO treatments may project a natural mode for the therapy of male infertility. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

    Directory of Open Access Journals (Sweden)

    Strazielle Nathalie

    2008-03-01

    Full Text Available Abstract Background Prostaglandin E2 (PGE2 is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation. Methods The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection. Results The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma. Conclusion The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.

  3. Modulatory role of Pterocarpus santalinus against alcohol-induced liver oxidative/nitrosative damage in rats.

    Science.gov (United States)

    Bulle, Saradamma; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Maturu, Paramahamsa; N Ch, Varadacharyulu

    2016-10-01

    Pterocarpus santalinus, a traditional medicinal plant has shown protective mechanisms against various complications. The aim of the present study is to evaluate therapeutic efficacy of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced oxidative/nitrosative stress leading to hepatotoxicity. In-vitro studies revealed that PSE possess strong DPPH (1,1-diphenyl-2-picryl hydrazyl) and nitric oxide radical scavenging activity. For in vivo studies male albino Wistar rats were treated with 20% alcohol (5g/kg b.wt/day) and PSE (250mg/kg b.wt/day) for 60days. Results showed that alcohol administration significantly altered plasma lipid profile with marked increase in the levels of plasma transaminases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (γGT). Moreover, lipid peroxides, nitric oxide (NOx) levels in plasma and liver were increased with increased iNOS protein expression in liver was noticed in alcohol administered rats and these levels were significantly brought back close to normal level by PSE administration except iNOS protein expression. Alcohol administration also decreased the content of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-s transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in liver, which were significantly enhanced by administration of PSE. The active compounds pterostilbene, lignan and lupeols present in PSE might have shown protection against alcohol-induced hepatic damage by possibly reducing the rate of lipid peroxidation, NOx levels and increasing the antioxidant defence mechanism in alcohol administered rats. Both biochemical and histopathological results in the alcohol-induced liver damage model emphasize beneficial action of PSE as a hepatoprotective agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Variable effect of ghrelin administration on pancreatic development in young rats. Role of insulin-like growth factor-1.

    Science.gov (United States)

    Dembiński, A; Warzecha, Z; Ceranowicz, P; Bielański, W; Cieszkowski, J; Dembiński, M; Pawlik, W W; Kuwahara, A; Kato, I; Konturek, P C

    2005-12-01

    Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been primarily isolated from the human and rat stomach. Ghrelin has been shown to stimulate appetite and fat deposition in adult rats and humans. The aim of this study was to investigate the effect of ghrelin administration on pancreatic growth in suckling, weaned and peripubertal seven week old rats. Rats were treated with saline or ghrelin (4, 8 or 16 nmol/kg/dose) intraperitoneally twice a day: suckling rats were treated for 7 or 14 days starting from the first postnatal day, three week old weaned rats and seven weeks old rats were treated for 5 days. Treatment with ghrelin did not affect animal weight in suckling or weaned rats, whereas in young seven week old rats, ghrelin caused a significant increase in body weight. Ghrelin decreased food intake in weaned rats; whereas in seven week old rats, food intake was enhanced. In suckling rats, ghrelin decreased the pancreatic weight, pancreatic amylase content, DNA synthesis and DNA content. In contrast, ghrelin increased pancreatic weight, DNA synthesis, DNA content and amylase content in weaned or young seven week old rats. Pancreatic blood flow was not affected by ghrelin in any group of rats tested. Ghrelin increased serum level of growth hormone in all rats. This effect was weak in suckling rats, higher in weaned and the highest in seven week old animals. Ghrelin did not affect serum level of insulin-like growth factor-1 (IGF-1) in suckling rats. In weaned and in seven week old rats, treatment with ghrelin caused increase in serum level of IGF-1. We conclude that ghrelin reduces pancreatic growth in suckling rats; whereas in weaned and young seven week old animals, treatment with ghrelin increases pancreatic growth. This biphasic effect of ghrelin in young animals on pancreatic growth seems to be related to age-dependent changes of the release of anabolic IGF-1.

  5. Neuroprotective role of heat shock protein 70 in the rostral ventrolateral medulla during acute mevinphos intoxication in the rat.

    Science.gov (United States)

    Chang, Chi; Chang, Alice Y W; Chan, Samuel H H

    2004-01-01

    Heat shock protein (HSP) is a family of highly conserved proteins that respond to stress and participate actively in cytoprotection. Within the HSP family, HSP70 is the major inducible member that confers protection against cell death. This study investigated whether HSP70 plays a neuroprotective role at the rostral ventrolateral medulla (RVLM), the origin of sympathetic neurogenic vasomotor tone in the medulla oblongata where the organophosphate insecticide mevinphos (Mev) acts to elicit cardiovascular toxicity. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of Mev (960 microg/kg) induced a significant increase in the HSP70 level in the ventrolateral medulla during phase I ('pro-life' phase), and returned to baseline during phase II ('pro-death' phase) Mev intoxication. Compared to artificial cerebrospinal fluid, normal mouse serum (1:20), or sense hsp70 oligonucleotide (50 pmol) pretreatment, microinjection of an anti-HSP70 antiserum (1:20) or an antisense hsp70 oligonucleotide (50 pmol) bilaterally into the RVLM significantly increased mortality, shortened the duration of phase I intoxication and augmented the induced hypotension in rats that received Mev (960 microg/ kg, i.v.). These results suggest that HSP70 induced in the RVLM during Mev intoxication provides neuroprotection against the organophosphate poison via prevention of cardiovascular depression.

  6. Gestational exposure to cadmium alters crucial offspring rat brain enzyme activities: the role of cadmium-free lactation.

    Science.gov (United States)

    Liapi, Charis; Stolakis, Vasileios; Zarros, Apostolos; Zissis, Konstantinos M; Botis, John; Al-Humadi, Hussam; Tsakiris, Stylianos

    2013-11-01

    The present study aimed to shed more light on the effects of gestational (in utero) exposure to cadmium (Cd) on crucial brain enzyme activities of Wistar rat offspring, as well as to assess the potential protective/restorative role that a Cd-free lactation might have on these effects. In contrast to earlier findings of ours regarding the pattern of effects that adult-onset exposure to Cd has on brain AChE, Na(+),K(+)- and Mg(2+)-ATPase activities, as well as in contrast to similar experimental approaches implementing the sacrificing mode of anaesthesia, in utero exposure to Cd-chloride results in increased AChE and Na(+),K(+)-ATPase activities in the newborn rat brain homogenates that were ameliorated through a Cd-free lactation (as assessed in the brain of 21-day-old offspring). Mg(2+)-ATPase activity was not found to be significantly modified under the examined experimental conditions. These findings could provide the basis for a further evaluation of the herein discussed neurotoxic effects of in utero exposure to Cd, in a brain region-specific manner.

  7. The role of endogenous nitric oxide and platelet-activating factor in hypoxia-induced intestinal injury in rats.

    Science.gov (United States)

    Caplan, M S; Hedlund, E; Hill, N; MacKendrick, W

    1994-02-01

    Nitric oxide is an endothelium-derived relaxing factor that promotes capillary integrity, inhibits leukocyte adherence and activation, and scavenges oxygen radicals. Because these effects are important in experimental intestinal injury, we studied the role of NO inhibition on hypoxia-induced bowel necrosis in the rat and investigated the interaction between platelet-activating factor (PAF) and NO in this model. Sprague-Dawley rats were treated with either hypoxia, NO synthase inhibition (NG-methyl-L-arginine [LNMA] or NG-nitro-L-arginine methyl ester [L-NAME]), hypoxia+LNMA, hypoxia+LNMA+NO donors, or hypoxia+LNMA+PAF receptor inhibition. Evaluations included blood pressure, superior mesenteric artery blood flow, arterial blood gases, histological intestinal injury, intestinal myeloperoxidase activity, and intestinal PAF activity. We found that hypoxia alone for 90 minutes (10% O2, partial O2 pressure = 45 mm Hg) or LNMA alone had no detrimental effects. However, hypoxia+LNMA together caused hypotension, metabolic acidosis, intestinal injury, increased intestinal myeloperoxidase activity, and elevated intestinal PAF concentrations that were prevented by exogenous L-arginine. Furthermore, the hypotension and intestinal injury was prevented by PAF receptor blockade. We conclude that endogenous NO protects the intestine from hypoxia-induced inflammation and injury, and the balance between local PAF and NO modulates the outcome of hypoxia-stressed intestine.

  8. Neuroprotective role of antioxidant and pyranocarboxylic acid derivative against AlCl3 induced Alzheimer’s disease in rats

    Institute of Scientific and Technical Information of China (English)

    Sarabjeet Singh; Ramandeep Singh; Ajay S Kushwah; Gaurav Gupta

    2014-01-01

    Objective: To assess potential of quercetin and etodolac to treat oxidative stress in neuronal death and inflammation in Alzheimer’s disease of AlCl3 induced rat models. All results of this AlCl3 model are compared with those obtained in controls.Methods:Wistar rats, housed in a controlled environment were treated with aluminum chloride (4.2 mg/kg of body weight, i.p.) for 28 d rather than oral to ensure neurotoxic concentration in hippocampus and hypothalamic region, part highly active in memory control and cognition, while control group was injected with saline. Estimation of thiobarbituric acid reactive substance, superoxide dismutase, reduced glutathione and acetylcholine levels gave estimation of neuronal damage. Low (20 mg/kg and 25 mg/kg) and high (40 mg/kg and 50 mg/kg) doses of quercetin and etodolac were administered to the test groups respectively. Histopathology study was conducted to perform relative study.Results:Co-administration of quercetin and etodolac either alone or in combination prevented the changes in biochemical markers of Alzheimer’s disease, but significant results (P<0.05) were seen when a combination of two was administered at low dose levels. Good correlation was developed between chemical estimations and histopathology study.Conclusions:Our findings suggest a combined role of anti-oxidant and cyclooxygenase inhibitor in protection of neural degeneration and inflammation due to oxidative stress.

  9. Fumonisin contamination of a corn sample associated with the induction of hepatocarcinogenesis in rats-role of dietary deficiencies.

    Science.gov (United States)

    Gelderblom, W C A; Rheeder, J P; Leggott, N; Stockenstrom, S; Humphreys, J; Shephard, G S; Marasas, W F O

    2004-03-01

    A corn sample associated with a field outbreak of equine leukoencephalomalacia in Pennsylvania, USA, during 1983/1984 and induced hepatotoxic and hepatocarcinogenic effects when fed to male Fischer rats was analyzed mycologically and chemically for the presence of fumonisins (FB), hydrolysed FB derivatives and aflatoxins (AFB). Fusarium verticillioides was found to be the predominant fungal contaminant in the corn sample but Aspergillus flavus was also present. Trace amounts (0.1 microg/kg) of AFB(1) and AFB(2) and a total FB level of 33.5 mg/kg (FB(1):FB(2):FB(3) ratio of 9:2.3:1) were found. No hydrolysed FB derivatives or AFG(1) and AFG(2) were detected. Based on the chemical stability of the fumonisins in different corn cultures of F. verticillioides kept at 4 degrees C over a period of 13-20 years, a level of approximately 55 mg/kg of total FB is estimated in the original corn sample. A possible role of certain dietary constituents such as the high protein content and deficiencies in certain micronutrients is evaluated to address differences in the organ-specific toxicity of FB(1) in rats using commercial, semi-purified, purified and corn-only diets.

  10. Role of the Mitochondrial Calcium Uniporter in Rat Hippocampal Neuronal Death After Pilocarpine-Induced Status Epilepticus.

    Science.gov (United States)

    Wang, Cui; Xie, Nanchang; Wang, Yunlong; Li, Yulin; Ge, Xinjie; Wang, Menglu

    2015-08-01

    The mitochondrial calcium uniporter (MCU) is reportedly involved in oxidative stress, apoptosis, and many neurological diseases. However, the role of the MCU in epilepsy remains unknown. In this study, we found that the MCU inhibitor Ru360 significantly attenuated neuronal death and exerted an anti-apoptotic effect on rat hippocampal neurons after pilocarpine-induced status epilepticus (SE), while the MCU activator spermine increased seizure-induced neuronal death and apoptosis. In addition, Ru360 decreased the level of seizure-induced reactive oxygen species (ROS) in mitochondria isolated from rat hippocampi. Moreover, Ru360 restored the altered mitochondrial membrane potential and cytochrome c (CytC) release in epileptic hippocampi. However, spermine treatment exerted an opposite effect on seizure-induced ROS production and mitochondrial membrane potential alteration and CytC release compared with Ru360 treatment. Altogether, the findings of this study suggest that MCU inhibition exerts a neuroprotective effect on seizure-induced brain injury possibly through the mitochondria/ROS/CytC pathway.

  11. Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-α

    Directory of Open Access Journals (Sweden)

    M. Markelic

    2011-11-01

    Full Text Available The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes, induces apoptosis of endothelial cells (ECs in brown adipose tissue (BAT and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsulinaemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonealy for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-α revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone.

  12. Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats.

    Science.gov (United States)

    Tarasiuk, A; Berdugo-Boura, N; Troib, A; Segev, Y

    2011-10-01

    Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (psleep and slow-wave activity was reduced (pgrowth impairment (pgrowth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.

  13. Reproductive efficiency of rats whose mothers treated with lead acetate during lactation: role of vitamin E

    Directory of Open Access Journals (Sweden)

    W. H. Yousif

    2010-01-01

    Full Text Available Reproductive efficiency of young male and female rats yielded from mothers treated with lead acetate (10 mg/kg B.W and vitamin E as an antioxidant (500 mg/kg during lactation period was studied. 27 pregnant albino rats aged 4-5 months divided into 3 groups, the first group given 0.2 ml distilled water through oral intubations (control. The second group given lead acetate (10 mg/kg B.W, while the 3rd group given lead acetate (10 mg/kg B.W with vitamin E (500 mg/kg B.Wt. Lead acetate treatment did not cause significant difference (P>0.05 in young male rats body, testes, epididymal (head, tail, prostate gland, seminal vesicle weights, number of epidiymal sperms count, percentage of live/dead sperms and sperms abnormalities accompanied with a significant increase (P0.05 in ovary and uterus weights. Lead acetate with vit. E cause significant decrease (P<0.05 in body, testes, epididymal (head, body weights, number of epididymal sperm count, percentage of live/dead and sperm abnormalities. Concerning young female rats treated with lead acetate and vit E showed a significant decrease (P<0.05 in body, uterus weights with a significant increase (P<0.05 in the duration of vaginal opening. Histopathological study revealed changes in the testes such as desquemination in some epithelial lining of seminiferous tubules and sertoli cells. Undevelopment of localized area of some seminiferous tubules with blood vessels congestion in both testes and ovaries with hyperemia in ovarian stroma, increase in follicular cells, decrease in corpus luteum formation, degeneration of ovarian follicles and increase in ovarian adipose tissue. This study concluded that lead acetate can be transmitted through mother milk to their pups. The dose of lead acetate (10 mg/kg B.W was enough to make bad effects on both male and female reproductive systems. Vitamin E (as an antioxidant found to have no improving effect in treatment of lead acetate disturbances on reproductive systems of

  14. Dose dependent role of Emodin and BTB14431 in suspension colon cancer model in rats

    OpenAIRE

    Rogalla, Stephan; Pohlenz, Jana; Garcia, Vanessa; Koplin, Gerold; Fuehrer, Kirsten; Lun, Andreas; Dubiel, Wolfgang; Geier, Caroline F.; Braumann, Chris

    2014-01-01

    Background. An “In Silico 2D/3D Conformer Screening” for structural similar antitumor substances to Curcumin was carried out and the novel antrachinone BTB14431 was found. Emodin, contained in several Chinese medical plants and BTB14431 are known to be potential inhibitors of the COP9-signalosome - stabilizing the tumor suppressor protein p53. The aim of this study was to analyze the suppressing effects on colorectal cancer in a standardized rat model (WAG/Rij). Methods. A suspension of C...

  15. Ozone Therapy on Rats Submitted to Subtotal Nephrectomy: Role of Antioxidant System

    Directory of Open Access Journals (Sweden)

    José Luis Calunga

    2005-01-01

    Full Text Available Chronic renal failure (CRF represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy. Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks. Renal plasmatic flow (RPF, glomerular filtration rate (GFR, the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD and catalase (CAT showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone

  16. Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.

    Science.gov (United States)

    Hussy, N; Deleuze, C; Pantaloni, A; Desarménien, M G; Moos, F

    1997-08-01

    1. To evaluate the implication of taurine in the physiology of supraoptic neurones, we (i) investigated the agonist properties of taurine on glycine and GABAA receptors of supraoptic magnocellular neurones acutely dissociated from adult rats, using whole-cell voltage clamp, (ii) studied the effects of taurine and strychnine in vivo by extracellular recordings of supraoptic vasopressin neurones in anaesthetized rats, and (iii) measured the osmolarity-dependent release of endogenous taurine from isolated supraoptic nuclei by HPLC. 2. GABA, glycine and taurine evoked rapidly activating currents that all reversed close to the equilibrium potential for Cl-, indicating activation of Cl(-)-selective channels. Glycine-activated currents were reversibly blocked by strychnine (IC50 of 35 nM with 100 microM glycine), but were unaffected by the GABAA antagonist gabazine (1-3 microM). GABA-activated currents were reversibly antagonized by 3 microM gabazine, but not by strychnine (up to 1 microM). 3. Responses to 1 mM taurine were blocked by strychnine but not by gabazine and showed no additivity with glycine-induced currents, indicating selective activation of glycine receptors. Responses to 10 mM taurine were partially antagonized by gabazine, the residual current being blocked by strychnine. Thus, taurine is also a weak agonist of GABAA receptors. 4. In the presence of gabazine, taurine activated glycine receptors with an EC50 of 406 microM. Taurine activated at most 70% of maximal glycine currents, suggesting that it is a partial agonist of glycine receptors. 5. In vivo, locally applied strychnine (300 nM) increased and taurine (1 mM) decreased the basal electrical activity of vasopressin neurones in normally hydrated rats. The effect of strychnine was markedly more pronounced in water-loaded rats. 6. Taurine, which is concentrated in supraoptic glial cells, could be released from isolated supraoptic nuclei upon hyposmotic stimulation. Decreases in osmolarity of 15 and 30

  17. Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats

    Directory of Open Access Journals (Sweden)

    Lakhera Abhijeet

    2015-06-01

    Full Text Available Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies.

  18. Cytosolic purine 5'-nucleotidases of rat liver and human red blood cells: regulatory properties and role in AMP dephosphorylation.

    Science.gov (United States)

    Van den Berghe, G; Bontemps, F; Vincent, M F

    1988-01-01

    Of the various species of cellular 5'-nucleotidases, membranous, lysosomal and cytosolic, only the latter are likely to play a role in the physiologic dephosphorylation of the 5'-nucleoside monophosphates present in the cytoplasm. The necessity to preserve cellular ATP renders a strict control of the dephosphorylation as well as of the deamination of AMP mandatory, because both nucleotides are maintained in equilibrium by adenylate kinase. Our studies of cytosolic purine 5'-nucleotidases purified from rat liver and from human erythrocytes, reviewed in this presentation, have shown that both display complex kinetic properties. Both enzymes have markedly higher affinities for IMP and for GMP than for AMP. In addition, they are stimulated by nucleoside triphosphates, among them ATP and GTP, and inhibited by Pi. The erythrocytic purine 5'-nucleotidase is also stimulated by glycerate 2,3-bisphosphate. It could thus be expected that under conditions of ATP and GTP breakdown, particularly when accompanied by an increase in Pi, the dephosphorylation of AMP would be curtailed. To verify this hypothesis, experiments were performed with isolated rat hepatocytes and with human red blood cells. The rate of dephosphorylation of AMP was measured by following time-wise the production of adenosine in the presence of coformycin (or deoxycoformycin) and 5-iodotubercidin. The coformycins inhibit the deamination of adenosine into inosine by adenosine deaminase, and 5-iodotubercidin inhibits the recycling of adenosine into AMP by adenosine kinase. Upon induction of ATP catabolism by the addition of fructose to isolated rat hepatocytes, the dephosphorylation of AMP was nearly completely suppressed. In accordance with these results, the activity of the rat liver cytosolic 5'-nucleotidase, assayed in the presence of concentrations of substrate and effectors mimicking those measured in intact cells following the addition of fructose, was decreased as compared to control conditions. In

  19. Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Huang Tu; Jing-Xiang Song; Xiao-Jun Xue; Xian-Wei Guo; Yun-Xia Ma; Zhi-Yao Chen; Zhong-Dong Zou; Lie Wang

    2012-01-01

    AIM:To investigate the role and potential mechanisms of bone marrow mesenchymal stem cells (MSCs) in severe acute peritonitis (SAP).METHODS:Pancreatic acinar cells from Sprague Dawley rats were randomly divided into three groups:nonsodium deoxycholate (SDOC) group (non-SODC group),SDOC group,and a MSCs intervention group (i.e.,a co-culture system of MSCs and pancreatic acinar cells + SDOC).The cell survival rate,the concentration of malonaldehyde (MDA),the density of superoxide dismutase (SOD),serum amylase (AMS) secretion rate and lactate dehydrogenase (LDH) leakage rate were detected at various time points.In a separate study,Sprague Dawley rats were randomly divided into either an SAP group or an SAP + MSCs group.Serum AMS,MDA and SOD,interleukin (IL)-6,IL-10,and tumor necrosis factor (TNF)-α levels,intestinal mucosa injury scores and proliferating cells of small intestinal mucosa were measured at various time points after injecting either MSCs or saline into rats.In both studies,the protective effect of MSCs was evaluated.RESULTS:In vitro,The cell survival rate of pancreatic acinar cells and the density of SOD were significantly reduced,and the concentration of MDA,AMS secretion rate and LDH leakage rate were significantly increased in the SDOC group compared with the MSCs intervention group and the Non-SDOC group at each time point.In vivo,Serum AMS,IL-6,TNF-α and MAD level in the SAP + MSCs group were lower than the SAP group;however serum IL-10 level was higher than the SAP group.Serum SOD level was higher than the SAP group at each time point,whereas a significant betweengroup difference in SOD level was only noted after 24 h.Intestinal mucosa injury scores was significantly reduced and the proliferating cells of small intestinal mucosa became obvious after injecting MSCs.CONCLUSION:MSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium,promote the proliferation of enteric epithelium and repair of the mucosa

  20. Role of synaptic structural plasticity in impairments of spatial learning and memory induced by developmental lead exposure in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Yongmei Xiao

    Full Text Available Lead (Pb is found to impair cognitive function. Synaptic structural plasticity is considered to be the physiological basis of synaptic functional plasticity and has been recently found to play important roles in learning and memory. To study the effect of Pb on spatial learning and memory at different developmental stages, and its relationship with alterations of synaptic structural plasticity, postnatal rats were randomly divided into three groups: Control; Pre-weaning Pb (Parents were exposed to 2 mM PbCl2 3 weeks before mating until weaning of pups; Post-weaning Pb (Weaned pups were exposed to 2 mM PbCl2 for 9 weeks. The spatial learning and memory of rats was measured by Morris water maze (MWM on PND 85-90. Rat pups in Pre-weaning Pb and Post-weaning Pb groups performed significantly worse than those in Control group (p<0.05. However, there was no significant difference in the performance of MWM between the two Pb-exposure groups. Before MWM (PND 84, the number of neurons and synapses significantly decreased in Pre-weaning Pb group, but not in Post-weaning Pb group. After MWM (PND 91, the number of synapses in Pre-weaning Pb group increased significantly, but it was still less than that of Control group (p<0.05; the number of synapses in Post-weaning Pb group was also less than that of Control group (p<0.05, although the number of synapses has no differences between Post-weaning Pb and Control groups before MWM. In both Pre-weaning Pb and Post-weaning Pb groups, synaptic structural parameters such as thickness of postsynaptic density (PSD, length of synaptic active zone and synaptic curvature increased significantly while width of synaptic cleft decreased significantly compared to Control group (p<0.05. Our data demonstrated that both early and late developmental Pb exposure impaired spatial learning and memory as well as synaptic structural plasticity in Wistar rats.

  1. Role of RhoA in regulating the pump function of isolated lymphatics from hemorrhagic shock rats.

    Science.gov (United States)

    Si, Yong-Hua; Niu, Chun-Yu; Zhao, Zi-Gang; Zhang, Li-Min; Zhang, Yu-Ping

    2013-07-01

    The aim of this present study was to examine changes in RhoA protein levels and the role in RhoA in lymphatic contractility and reactivity after hemorrhagic shock. Levels of RhoA and phospho-RhoA in lymphatic tissue isolated from hemorrhagic shock rats were measured, and the contractility and reactivity to substance P of lymphatics isolated from control rats and rats subjected to shock 0.5 and 2 h were determined with an isolated lymphatic perfusion system at a transmural pressure of 3 cmH2O. At the same time, lymphatics isolated from rats subjected to shock 0.5 and 2 h were incubated with agonists and antagonists of RhoA/Rho kinase signaling. Contractile frequency, end-diastolic and end-systolic diameter, and passive diameter were recorded and used to calculate lymphatic tonic index, contractile amplitude, and fractional pump flow. After stimulation with a gradient of substance P, the differences between the preadministration and postadministration values of contractile frequency, contractile amplitude, tonic index, and fractional pump flow were calculated to further assess lymphatic reactivity. RhoA protein levels were significantly increased at 0.5 h after shock but decreased at 2 and 3 h after shock; p-Rho levels were initially increased after shock and subsequently decreased. The contractility and reactivity of 0.5-h-shocked lymphatics were significantly reduced by the RhoA antagonist C3 transferase and the Rho kinase antagonist Y-27632. The RhoA agonist U-46619 increased the contractility and reactivity of 2-h-shocked lymphatics, whereas Y-27632 suppressed the effect of U-46619. Okadaic acid, an inhibitor of myosin light-chain phosphatase, had no effect on the contractility of 2-h-shocked lymphatics, but improved lymphatic reactivity. These results suggest that RhoA is involved in the modulation of lymphatic pump function during hemorrhagic shock and that its effects may be mediated by Rho kinase and MLCP.

  2. Ozone protects rat heart against ischemia-reperfusion injury: A role for oxidative preconditioning in attenuating mitochondrial injury.

    Science.gov (United States)

    Meng, Weixin; Xu, Ying; Li, Dandan; Zhu, Erjun; Deng, Li; Liu, Zonghong; Zhang, Guowei; Liu, Hongyu

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a major cause of cardiac dysfunction during cardiovascular surgery, heart transplantation and cardiopulmonary bypass procedures. The purpose of the present study was to explore, firstly, whether ozone induces oxidative preconditioning by activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and, secondly, whether ozone oxidative preconditioning (OzoneOP) can protect the heart against IRI by attenuating mitochondrial damage. Rats were subjected to 30min of cardiac ischemia followed by 2h of reperfusion, with or without prior OzoneOP (100μg/kg/day) for 5 days. Antioxidant capacity, myocardial apoptosis and mitochondrial damage were evaluated and compared at the end of reperfusion. OzoneOP was found to increase antioxidant capacity and to protect the myocardium against IRI by attenuating mitochondrial damage and myocardial apoptosis. The study suggests a potential role for OzoneOP in protecting the heart against IRI during cardiovascular surgery, cardiopulmonary bypass procedures or transplantation.

  3. CARDIOPROTECTIVE ROLES OF THE CHINESE MEDICINAL FORMULA BAO-XIN-TANG ON ACUTE MYOCARDIAL INFARCTION IN RATS.

    Science.gov (United States)

    Wang, Yang; Wang, Weihao; Peng, Weijun; Liu, Weiping; Cai, Weijun; Xia, Zian; Zhang, Honggeng; Xing, And Zhihua

    2017-01-01

    Bao-Xin-Tang (BXT) is a traditional Chinese medicinal formula used for the treatment of coronary heart disease and known to have favorable therapeutic benefits. The current study was designed to determine whether BXT has a cardioprotective role for acute myocardial infarction. The underlying mechanisms were also explored. The Sprague-Dawley rat model of acute myocardial infarction was established by occluding the left anterior descending branch of the coronary artery. After a 3-h ischemic period, we determined the myocardial infarction size, inflammatory components, and antioxidant activities. The data showed that BXT could reduce the infarction size and lower the levels of C-reactive protein, interleukin-6, and myeloperoxidase, and increase the activities of superoxide dismutase and the anti-inflammatory cytokine, interleukin-10. These results indicate that administration of BXT, following acute myocardial infarction, could reduce infarct size. The effects of BXT may be related to its anti-inflammatory and anti-oxidative properties.

  4. Role of phyto-stabilised silver nanoparticles in suppressing adjuvant induced arthritis in rats.

    Science.gov (United States)

    Mani, Aparna; Vasanthi, C; Gopal, V; Chellathai, Darling

    2016-12-01

    The present study was aimed to evaluate the anti-arthritic effects of silver nanoparticles synthesised using Piper nigrum extract and to further establish its mechanism of action in a rat model of adjuvant induced arthritis (AA). Adjuvant arthritis was induced by injecting complete Freund's adjuvant (0.1mL) into the left hind paw of 36 albino Wistar rats (n=6). Silver nanoparticles stabilised with Piper nigrum extract (25 and 50mg/kg). Commercial silver nanoparticles (50mg/kg) and methotrexate (0.1mg/kg) were administered by intraperitoneal route from day 11 to day 22 on alternate days. It was found that treatment with silver nanoparticles stabilised with Piper nigrum (S-AgNPs) significantly reduced the paw edema and alleviated the histopathological changes of cell infiltration, synovial hyperplasia, bone and cartilage destruction. Furthermore, the phytostabilised silver nanoparticles (S-AgNPs) inhibited the protein expression of NF-kβ p65 and TNF-α as evidenced by immunohistochemistry analysis. Our current findings suggest that silver nanoparticles stabilised with Piper nigrum extract (S-AgNPs) have potent anti-arthritic activity which is mediated by inhibition of TNF-α and suppression of pro-inflammatory cytokines that are secreted in response to activated transcription factors of NF-kβ. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Role of Dopamine 2 Receptor in Impaired Drug-Cue Extinction in Adolescent Rats.

    Science.gov (United States)

    Zbukvic, Isabel C; Ganella, Despina E; Perry, Christina J; Madsen, Heather B; Bye, Christopher R; Lawrence, Andrew J; Kim, Jee Hyun

    2016-06-01

    Adolescent drug users display resistance to treatment such as cue exposure therapy (CET), as well as increased liability to relapse. The basis of CET is extinction learning, which involves dopamine signaling in the medial prefrontal cortex (mPFC). This system undergoes dramatic alterations during adolescence. Therefore, we investigated extinction of a cocaine-associated cue in adolescent and adult rats. While cocaine self-administration and lever-alone extinction were not different between the two ages, we observed that cue extinction reduced cue-induced reinstatement in adult but not adolescent rats. Infusion of the selective dopamine 2 receptor (D2R)-like agonist quinpirole into the infralimbic cortex (IL) of the mPFC prior to cue extinction significantly reduced cue-induced reinstatement in adolescents. This effect was replicated by acute systemic treatment with the atypical antipsychotic aripiprazole (Abilify), a partial D2R-like agonist. These data suggest that adolescents may be more susceptible to relapse due to a deficit in cue extinction learning, and highlight the significance of D2R signaling in the IL for cue extinction during adolescence. These findings inspire new tactics for improving adolescent CET, with aripiprazole representing an exciting potential pharmacological adjunct for behavioral therapy.

  6. Role of central histaminergic system in lorazepam withdrawal syndrome in rats.

    Science.gov (United States)

    Nath, C; Gupta, M B

    2001-04-01

    Effects of histaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam-dependent rats. Physical dependence was developed by giving lorazepam admixed with the food in the following dose schedule (in mg/kg given daily x days): 10 x 4, 20 x 4, 40 x 4, 80 x 4, and 120 x 7. The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot shock aggression (FSA), and audiogenic seizures. During the withdrawal period, the rats were divided into groups of 10 each. Control-withdrawal group did not receive any drug. The drugs (in mg/kg administered intramuscularly)--L-histidine (50), histamine-N-methyl (2), promethazine (10), pheniramine (10), astemizole (10), and thioperamide (1)--were given separately in other groups daily during the withdrawal period. The withdrawal signs in control group were hyperkinesia, hyperaggression, and audiogenic seizures. L-Histidine, precursor of histamine, and thioperamide, antagonist of H3 receptor, potentiated hyperkinesia, hyperaggression, and audiogenic seizures. Histamine-N-methyl, agonist of H3 receptor, and H1 receptor antagonists, promethazine and phen