NITRIC OXIDE AND ALLYL ALCOHOL INDUCED HEPATOTOXICITY

Abstract

<p><strong>Background.</strong> Nitric oxide (NO) is an important mediator of hepatotoxicity. NO in liver can be derived from two sources: (1) constitutive NO synthase (eNOS) in endothelial cells, and (2) inducible NO synthase (iNOS) in hepatocytes and Kupffer cells.<br /><strong>Objectives.</strong> The present study was aimed to examine the effect of nonselective NOS inhibitor (L-NAME) and selective iNOS inhibitor (1400W) on the development of allyl alcohol (AA) induced hepatitis in rats.<br /><strong>Methods.</strong> Male Wistar rats were treated with intraperitoneal injection of saline or AA and L-NAME or 1400W. NO in liver was measured by electrochemical method after eNOS stimulation by calcium ionophore. Total NOS activity and nitrite/nitrate content were measured in liver and blood serum. The activity of free radical oxidation in liver was measured by chemiluminescent method. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed in blood serum<br /><strong>Results.</strong> AA increased the activity of free radical processes in liver and markers of cytolysis in serum, as well as decreased eNOS and increased iNOS activities. L-NAME considerably inhibited eNOS and augmented the necrosogenic properties of AA, whereas 1400W partially prevented liver damage.<br /><strong>Conclusion.</strong> It has been concluded that in AA intoxication NO produced from eNOS is beneficial to the liver, but NO derived from the upregulated iNOS has deleterious effect.</p><p><strong>KEY WORDS:</strong> nitric oxide, toxic hepatitis, NOS inhibitors.<br /><br /></p>