NITROARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, PREVENTS CHANGES IN SUPEROXIDE RADICAL AND ANTIOXIDANT ENZYMES INDUCED BY AMMONIA INTOXICATION

Injection of large doses of ammonium salts leads to the rapid death of animals. However, the molecular mechanisms involved in ammonia toxici ty remain to be clarified. We reported that injecting ammonium acetate (7 mmol/kg) to rats increases the production of superoxide and reduce s the activities of some antioxidant enzymes in rat liver and brain. W e proposed that these effects induced by ammonia intoxication would be mediated by formation of nitric oxide. To test this possibility we te sted whether injection of nitroarginine, an inhibitor of nitric oxide synthase, prevents the effects of ammonia intoxication on antioxidant enzymes and superoxide formation. Following injection of ammonia, glut athione peroxidase, superoxide dismutase and catalase activities were decreased in liver by 42%, 54% and 44%, respectively. In brain these a ctivities were reduced by 35%, 46% and 65%, respectively. Glutathione reductase remained unchanged. Superoxide production in submitochondria l particles from liver and brain was increased by more than 100% in bo th tissues. Both reduction of activity of antioxidant enzymes and incr eased superoxide radical production were prevented by previous injecti on of 45 mg/kg of nitroarginine, indicating that ammonia induces incre ased formation of nitric oxide, which in turn reduces the activity of antioxidant enzymes, leading to increased formation of superoxide.