imai yoichiro

We examined whether water-immersion restraint stress (WIRS) disrupts nonenzymatic antioxidant defense systems through ascorbic acid depletion in the adrenal gland of rats. Rats were exposed to WIRS for 0.5, 1.5, 3 or 6h. WIRS increased serum adrenocorticotropic hormone, corticosterone and glucose concentrations and adrenal corticosterone content at each time point. WIRS increased adrenal lipid peroxide content at 3 and 6h, and the increase was twofold higher than the unstressed level at 6h. WIRS decreased adrenal ascorbic acid content at each time point, and the decrease reached one-third of the unstressed level at 6h. WIRS increased adrenal reduced glutathione content at 0.5 and 6h but reduced that content to half of the unstressed level at 6h. WIRS increased adrenal -tocopherol content at 1.5h but returned that content to the unstressed level thereafter. When rats with 6h of WIRS was orally preadministered with l-ascorbic acid (250mg/kg), WIRS-induced changes in adrenal lipid peroxide, ascorbic acid and reduced glutathione contents were attenuated without any change in stress response. These results indicate that WIRS disrupts nonenzymatic antioxidant defense systems through rapid and continuous ascorbic acid depletion in the adrenal gland of rats. Copyright (c) 2012 John Wiley & Sons, Ltd.

We examined the effect of vitamin E depletion on liver oxidative damage in rats with water-immersion restraint stress (WIRS). Male Wistar rats were fed a normal diet (N) or vitamin E-depleted diet (VE-D) for 4 wk. N- and VE-D-fed rats were exposed to WIRS for 6 h. The activities of serum transaminases and lactate dehydrogenase and serum ascorbic acid concentration were similar in both diet groups. WIRS exposure increased these serum enzyme activities and the serum ascorbic acid concentration in both diet groups but the ratios of these increases were higher in VE-D-fed rats than in N-fed rats. Serum and liver a-tocopherol concentrations in VE-D-rats were approximately 50% and 30% of those in N-fed rats, respectively. WIRS exposure reduced liver alpha-tocopherol concentration in VE-D-fed rats, but not in N-fed rats. Liver ascorbic acid and reduced glutathione concentrations were higher in the VE-D-fed group than in the N-fed group. WIRS exposure reduced liver ascorbic acid and reduced glutathione concentrations in both diet groups. There were no differences in liver concentrations of coenzyme Q(9) or coenzyme Q(10) in the reduced form between the N- and VE-D-fed groups. WIRS exposure reduced liver concentrations of coenzyme Q(9) and coenzyme Q(10) in the reduced form in both diet groups. Liver lipid peroxide concentration was higher in the VE-D-fed group than in the N-fed group. WIRS exposure raised liver lipid peroxide concentration more in the VE-D-fed group than in the N-fed group. These results indicate that vitamin E depletion enhances liver oxidative damage in rats with WIRS.

We examined whether non-enzymatic antioxidant defense systems are disrupted in the brain of rats with water-immersion restraint stress. When rats were exposed to water-immersion restraint stress for 1.5, 3 or 6 h, the brain had decreased ascorbic acid and reduced glutathione contents and increased lipid peroxide and nitric oxide metabolites contents at 3 h and showed further changes in these components with a reduction of vitamin E content at 6 h. Increased serum levels of stress markers were found at 1.5, 3 or 6 h of WIRS. Oral pre-administration of L-ascorbic acid (1.5 mmol/kg) or vitamin E (0.5 mmol/kg) to rats with 6 h of water-immersion restraint stress attenuated the increases in lipid peroxide and nitric oxide metabolites contents and the decrease in vitamin E content in the brain. Pre-administered L-ascorbic acid attenuated the decreases in brain ascorbic acid and reduced glutathione contents at 6 h of water-immersion restraint stress, while pre-administered vitamin E enhanced the decreases in those contents. Pre-administered L-ascorbic acid or vitamin E did not affect the increased serum levels of stress markers in rats with 6 h of water-immersion restraint stress. These results indicate that water-immersion restraint stress causes disruption of nonenzymatic antioxidant defense systems through enhanced lipid peroxidation and nitric oxide generation in the brain of rats with water-immersion restraint stress.

Objectives: We examined whether a single exposure of rats to water-immersion restraint stress (WIRS) induces oxidative stress in the thymus and spleen. Methods: Vitamin E, ascorbic acid, reduced glutathione (GSH), and lipid peroxide (LPO) were assayed in the thymus and spleen of rats with and without 6 hours of WIRS. Results: In unstressed rats, vitamin E, ascorbic acid, GSH, and LPO levels were higher in the thymus than in the spleen. Thymic ascorbic acid level was lower in stressed rats than in unstressed rats. Splenic ascorbic acid level was similar in both groups. Thymic and splenic GSH levels were lower in stressed rats than in unstressed rats but the reduced amount of GSH was lower in the spleen than in the thymus. Thymic vitamin E level was lower in stressed than in unstressed rats. Splenic vitamin E level was higher in stressed rats than in unstressed rats. Thymic and splenic LPO levels were higher in stressed rats than in unstressed rats but the increased amount of LPO was higher in the thymus than in the spleen. Conclusion: It is indicated that a single expose of rats to WIRS induces oxidative stress more severely in the thymus than in the spleen.

We examined whether L-ascorbic acid (AA) (or reduced ascorbic acid) protects against oxidative damage in the liver of rats subjected to water-immersion stress (WIRS). AA (100, 250 or 500 mg/kg) was orally administered at 0.5 h before the onset of WIRS. Rats with 6 h of WIRS had increased serum corticosterone, glucose, total ascorbic acid (T-AA), AA, lipid peroxide (LPO), and NOx concentrations and alanine aminotransferase and aspartate aminotrasferase activities. The stressed rats had increased hepatic LPO, NOx, and dehydroascorbic acid concentrations and myeloperoxidase activity, decreased hepatic T-AA, AA, reduced glutathione concentrations and superoxide dismutase activity, and unchanged hepatic vitamin E concentration. Pre-administered AA attenuated the stress-induced changes in serum LPO and NOx concentrations and alanine aminotransferase and aspartate aminotrasferase activities and hepatic LPO, NOx, and T-AA, AA, dehydroascorbic acid, and reduced glutathione concentrations and myeloperoxidase and superoxide dismutase activities dose-dependently. Pre-administered AA did not affect the stress-induced changes in serum corticosterone and glucose concentrations. These results indicate that pre-administered AA protects against oxidative damage in the liver of rats with WIRS possibly by attenuating disruption of the antioxidant defense system and increases in NO generation and neutrophil infiltration in the tissue.

Rats were intraperitoneally treated once with compound 48/80 (C48/80), a mast cell degranulator, (0.75 mg/kg). Serum serotonin, histamine and corticosterone levels increased 0.5 h after C48/80 treatment, but their increases were reduced thereafter. Adrenal total ascorbic acid (ascorbic acid plus dehydroascorbic acid), ascorbic acid and clehydroascorbic acid levels decreased 0.5, 3 or 6 h after C48/80 treatment, adrenal lipid peroxide level increased at 3 and 6 h, adrenal non-protein-SH level decreased at 3 and 6 h and adrenal beta-tocopherol level decreased at 3 h. Ketotifen, a mast cell stabilizer (I mg/kg) administered intraperitoneally at 0.5 h before C48/80 treatment, attenuated all these changes found in the serum and adrenal at 3 h after treatment, while beta-tocopherol (250 mg/kg), administered orally at 0.5 h after C48/80 treatment, attenuated all these changes in the adrenal tissue. These results indicate that C48/80 causes oxidative stress in rat adrenal gland through mast cell degranulation.

In this study, we examined the protective effects of vitamin E (VE) against gastric mucosal lesions induced by water immersion restraint stress (WIRS) in rats in comparison with that of vitamin C (VC). The gastric mucosa of rats with 6 h of WIRS showed lesions with bleeding, decrease in nonprotein SH, VC, VE, and adherent mucus concentrations and constitutive nitric oxide synthase activity, and increase in lipid peroxide and NOx (nitrite/nitrate) concentrations and myeloperoxidase, xanthine oxidase, and inducible nitric oxide synthase activities. Either VE (0.05 or 0.5 mmol/kg) or VC (0.5 or 1.5 mmol/kg) was orally administered to rats with 6 h of WIRS just before the onset of the stress. Both doses of preadministered VE prevented gastric mucosal lesion development and attenuated all these changes in gastric mucosal components and enzymes studied, whereas only the higher dose of preadministered VC suppressed the changes in all parameters studied. These results indicate that orally administered VE protects against WIRS-induced gastric mucosal lesions in rats more effectively than orally administered VC. These results also suggest that the administered VE protects against gastric mucosal lesions in rats with WIRS through its antioxidant and anti-inflammatory actions in the gastric mucosa in the same way as the administered VC. (C) 2010 International Union of Biochemistry and Molecular Biology, Inc.

The plasma or serum levels of various enzymes and components are known to increase in rats with water-immersion restraint stress (WIRS). We examined whether oxidative stress is involved in increases in the serum levels of various enzymes and components in rats with WIRS. Rats were exposed to WIRS for 6 h after oral administration of vitamin E (VE) (50 or 250 mg/kg). Rats with WIRS had increased serum alanine aminotransferase, aspartate aminotranseferase, lactate dehydrogenase, creatine kinase, urea nitrogen, creatinine, glucose, corticosterone, adrenocorticotropic hormone and lipid peroxide (LPO) levels, increased kidney and heart VE levels, decreased skeletal muscle VE level, and increased LPO levels in all tissues studied. Pre-administered VE (50 or 250 mg/kg) attenuated the increased serum alanine amino-transferase, aspartate aminotranseferase, lactate dehydrogenase, creatine kinase, urea nitrogen, creatinine, and LPO levels, the decreased skeletal muscle VE level, and the increased LPO levels in all tissues studied more effectively at its higher dose than at its lower dose. However, either dose of the pre-administered VE did not affect the increased serum glucose, corticosterone, and adrenocorticotropic hormone levels. These results suggest that oxidative stress is involved in increases in the serum levels of various enzymes and components in rats with WIRS.