Abstract: In this study, the effects of the nitric oxide donor isosorbide dinitrate (ISDN) and the nitric oxide precursor L-arginine on oxidative stress and histopathological changes induced by 96% ethanol in the brain, liver and gastric tissue were examined. Rats were treated with either ISDN (5 or 10 mg/kg) or L-arginine (200 or 400 mg/kg), given orally 30 min before ethanol (1.5 ml, p.o.) and euthanized 2h after ethanol administration. Oxidative stress biomarkers; malondialdehyde, reduced glutathione, nitric oxide and paraoxonase-1 activity were determined in brain and liver. In addition, brain, liver and gastric mucosal histopathology was done. Results showed that ethanol treated rats exhibited a significant elevation in levels of malondialdehyde (lipid peroxidation), and nitric oxide along with a significant decrease in reduced glutathione and paraoxonase-1 activity in brain and liver tissue. ISDN or L-arginine given prior to ethanol -treated animals, resulted in a significant decrease in malondialdehyde and nitric oxide in a dose-dependent manner. Moreover, a significantly raised reduced glutathione levels and paraoxonase-1 activities in both the brain and liver were observed with respect to ethanol control values. The histological study indicated that either ISDN or L-arginine protected against brain, liver and gastric mucosal damage. These data provide evidence that ISDN and L-arginine could protect against the toxic effects of ethanol by attenuating oxidative stress.

Keywords: nitric oxide donors, ethanol hepatotoxicity, gastric ulcer, neurotoxicity, L-arginine, isosorbide dinitrate

Pages: 61-76

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