Influence of L-arginine on Cisplatin-Induced Hepatotoxicity in both normally Fed and Protein Malnourished Rats

Abstract

Liver has great capacity to detoxify toxic substances and synthesized useful principles. Therefore, damage to the liver inflicted by hepatotoxic agents is of grave consequences. Protein malnutrition produces profound effects on biochemistry and physiology of the body as well as growth failure of most body organs. Cisplatin is a member of anticancer drugs that elicits many hepatotoxicity. The study was carried out to investigate the possible hepato-curative and hepato-protective effect of l-arginine either alone or in combination with silymarin against hepatotoxicity resulted from cisplatin (7.5 mg/kg i.p.) treatment in normally fed and protein malnourished male albino rats. All treatments were administered for 5 consecutive days (l-arginine, 200 mg/kg i.p.) and (silymarin, 100 mg/kg i.p.) after and before cisplatin injection. In the cisplatin group, the results revealed significant decrease in the body weight and increase in alanine aminotransferase and aspartate aminotransferase, as well as liver body weight ratio. Antioxidant status was suppressed as manifested by significant decline in reduced glutathione content and total protein level along with decreased enzymatic activity of super oxide dismutase and increased lipid peroxidation, nitric oxide, an effect that was enhanced by combination with protein malnutrition. Administration of l-arginine was effective in decreasing cisplatin hepatotoxicity that restore of anti-oxidant machinery and blunting of mounted malondialdehyde levels. Moreover, histological examination demonstrated that l-arginine significantly reduced cellular infiltration, congestion blood vessels, degenerative changes in hepatocytes and fatty changes. It is concluded that the combined administration of l-arginine with silymarin represents a promising strategy to restrain the cisplatin hepatotoxicity.