Protective Effect of Captopril against 5- Fluorouracil-Induced Hepato and Nephrotoxicity in Male Albino Rats

Abstract

5-fluorouracil (5-FU) is a potent anticancer agent; its clinical use is limited for its marked hepatotoxicity and nephrotoxicity. The present study investigated the possible protective effect of captopril, an angiotensinconverting enzyme (ACE) inhibitor, on 5-FU-induced hepatotoxicity and nephrotoxicity in male albino rats. 5-FU 20mg/kg b.wt injected i.p. caused a significant increase in serum urea, creatinine, uric acid, corteisol, and glucose levels, respectively. Also, a marked elevation in potassium (K), bilirubin, α AFP, alanine aminotransferase (ALT), aspartat aminotransferase (AST) and malondialdehyde (MDA). 5-FU caused a significant decrease in Sodium (Na), magnesium (Mg), glutathione (GSH), protein and albumin. Captopril 20mg/kg b.wt. administered 1h before 5-FU ameliorated the biochemical toxicity induced by 5-FU, in the kidney and liver. This was evidenced by a significant reduction in serum urea, creatinine, uric acid, corteisol, glucose levels, K, bilirubin, α AFP,ALT and AST, respectively, and a significant restoration in Na, Mg, GSH, protein and albumin. These results indicate that captopril, an Angiotensin-converting enzyme ACE activity, has a protective effect against 5-FU-induced damage to kidney and liver. This reflects the beneficial role of captopril in treatment of renovascular hypertention and congestive liver failure.