EVALUATION OF THE POSSIBLE PROTECTIVE EFFECTS OF CAPTOPRIL AND VALSARTAN ON METHOTREXATE-INDUCED HEPATOTOXICITY IN ALBINO RATS

Sanaa A. Ahmed*, Wafaa A. Abd Elaa and Mayada M. Ahmed

ABSTRACT

The aim of this study was to evaluate the ameliorating effect of both captopril and valsartan on methotrexate (MTX)-induced hepatotoxicity in rats. Forty two adult male albino rats weighing 180-250 g were divided into 6 groups; n= 7. Groups 1, 2, and 3 were orally received saline (control), captopril (20 mg/kg/day) and valsartan (30 mg/kg/day) respectively for 3 weeks. Groups 4, 5, and 6 were orally pretreated with saline (toxicity control), captopril and valsartan respectively in the same doses and duration as three previous groups. At the end of treatment, groups 4, 5, and 6 were subjected to single dose of MTX 5 mg/kg I.P. The impacts of MTX on the hepatic injury and its prevention by captopril and valsartan were assessed by estimation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T.Bil), total protein and albumin. In addition, superoxide dismutase (SOD) activity, nitric oxide (NO), malondialdehyde (MDA) levels were measured in serum and liver homogenates. MTX resulted in significant increases (P < 0.01) in AST, ALT T.Bil, NO and MDA levels and decrease in serum albumin and protein levels and SOD activity; as well as severe congestion and inflammation in liver tissues compared to control group. On the other hand, pre-treatment with captopril or valsartan decreased MTX-induced alterations in liver function, NO, and MDA levels and SOD activity; also, ameliorated the induced changes in liver tissues. The oxidative stress plays an essential role in MTX-induced hepatotoxicity in rats. Captopril and valsartan have a protective effect on MTX-induced hepatotoxicity; which may be created by their antioxidant effect.

Keywords: Captopril, Valsartan, Methotrexate, Hepatotoxicity, SOD and NO.