Beneficial effect of nitric oxide synthase inhibitor on hepatotoxicity induced by allyl alcohol

Department of Pharmacology, College of Pharmacy, King Saud UniversityThe effect of aminoguanidine (a selective inhibitor of inducible nitric oxide synthase) on allyl alcohol-induced liver injury was assessed by the measurement of serum ALT and AST activities and histopathological examination. When aminoguanidine (50– 300 mg/kg, i.p.) was administered to mice 30 min before a toxic dose of allyl alcohol (75 mL/kg, i.p.), significant changes related to liver injury were observed. In the presence of aminoguanidine the level of ALT and AST enzymes were significantly decreased. All symptoms of liver necrosis produced by allyl alcohol toxicity almost completely disappeared when animals were pretreated with aminoguanidine at 300 mg/kg. Depletion of hepatic glutathione as a consequence of allyl alcohol metabolism was minimal in mice pretreated with aminoguanidine at 300 mg/kg. It was found that the inhibition of toxicity was not due to alteration in allyl alcohol metabolism since aminoguanidine did not effect alcohol dehydrogenase activity both in vivo and in vitro

Protective effect of aminoguanidine, a nitric oxide synthase inhibitor, against carbon tetrachloride induced hepatotoxicity in mice

The present study was undertaken to evaluate the effect of aminoguanidine (AG) on carbon tetrachloride (CCU)-induced hepatotoxicity. Treatment of mice with CCU (20 pl/kg, i.p.) resulted in damage to centrilobular regions of the liver, increase in serum aminotransferase and rise in lipid peroxides level 24 hours after CCU administration. Pretreatment of mice with AG (50 mg/kg, i.p.) 30 minutes before CCU was found to protect mice from the CCU-induced hepatic toxicity. This protection was evident from the significant reduction in serum aminotransferase, inhibition of lipid peroxidation and prevention of CCU-induced hepatic necrosis revealed by histopathology. Aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase, did not inhibit the in vitro lipid peroxidation. Taken together, these data suggest a potential role of nitric oxide as an important mediator of CCU-induced hepatotoxicity.Corresponding Author: Dr. Othman A. Al-Shabanah, Ph.D. Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Email: [email protected]

Neo-nitro-l-arginine methylester ameliorates myocardial toxicity induced by doxorubicin

The effects of Nω-nitro-L-arginine methylester (L-NAME) and L-arginine on cardiotoxicity that is induced by doxorubicin (Dox) were investigated. A single dose of Dox 15 mg/kg i.p. induced cardiotoxicity, manifested biochemically by a significant elevation of serum creatine phosphokinase (CPK) activity [EC 2.7.3.2]. Moreover, cardiotoxicity was further confirmed by a significant increase in lipid peroxides, measured as malon-di-aldehyde (MDA) in cardiac tissue homogenates. The administration of L-NAME 4 mg/kg/d p.o. in drinking water 5 days before and 3 days after the Dox injection significantly ameliorated the cardiotoxic effects of Dox, judged by the improvement in both serum CPK activity and lipid peroxides in the cardiac tissue homogenates. On the other hand, the administration of L-arginine 70 mg/kg/d p.o. did not protect the cardiac tissues against the toxicity that was induced by the Dox treatment. The findings of this study suggest that L-NAME can attenuate the cardiac dysfunction that is produced by the Dox treatment via the mechanism(s), which may involve the inhibition of the nitric oxide (NO) formation. L-NAME may, therefore, be a beneficial remedy for cardiotoxicity that is induced by Dox and can then be used to improve the therapeutic index of Dox