Nitro-arginine methyl ester, a non-selective inhibitor of nitric oxide synthase reduces ibuprofen-induced gastric mucosal injury in the rat

Abstract

Ibuprofen is a commonly used non-steroidal anti-inflammatory drug. Gastrointestinal adverse drug reactions from ibuprofen usage include gastric mucosal ulcers and bleeding. The mechanism by which ibuprofen induces gastric mucosal damage is not clear. The present study is an attempt to examine the role of nitric oxide in the pathogenesis of ibuprofen-induced gastric mucosal damage. Ibuprofen administered orally at the dose of 100 mg/kg body weight for 6 days to the rats resulted in gastric mucosal injury. Serum nitrite and nitrosothiol were increased significantly as compared with the controls, which were treated with the vehicle alone. In the gastric mucosa, lipid peroxidation and protein thiols were increased, and the activity of glyceraldehyde 3-phosphate dehydrogenase, a nitric oxide sensitive enzyme was decreased significantly. Pretreatment of the rats daily with nitric oxide synthase inhibitor, nitro-arginine methyl ester (30 mg/kg body weight) 1 hr before treatment with ibuprofen reduced the gastric mucosal injury. Biochemically, it prevented the rise in serum nitrite levels and the increase in lipid peroxidation and protein thiol levels and the loss of glyceraldehyde 3-phosphate dehydrogenase activity in the gastric mucosa. The results of the present study suggest that increased nitric oxide production may be one of the mechanisms by which ibuprofen produces gastric mucosal injury and that inhibition of nitric oxide synthase reduces gastric mucosal injury.