protective role of the angiotensin-converting enzyme inhibitor enalapril against gamma radiation induced organ toxicity in the rat

ABSTRACT

The present study was designed to evaluate the radioprotective efficacy of the angiotensin-converting enzyme inhibitor enalapril and the possible mechanisms of this radioprotection. This included the ability of prophylactic enalapril treatment to prevent or retard gamma radiation-induced organ toxicity and to protect tissue' antioxidant enzymes in the rat. Prior to irradiation rats were randomized to groups receiving enalapril or no treatment, in addition to a control group of non-irradiated, non-treated rats. Enalapril was administered intraperitoneally [0.1 mg/ kg body weight / day], 4 weeks before and 12 weeks after irradiation. Both groups were exposed to a single dose of 7GY gamma radiation. Irradiation induced significant elevations in the levels of blood urea nitrogen and serum creatinine and serum activities of lactate dehydrogenase [LDH], creatine kinase [CK], alanine amino transferase [ALT] and aspartate amino transferase [AST] compared to control values, indicative of renal, cardiac and hepatic injury. Also there was an increase in the serum levels of triglycerides, total cholessterol and LDL-cholesterol. On the contrary, HDL-cholesterol level was decreased. The heart, kidney and liver antioxidant enzymes including total glutathione peroxidase [total-GPX], glutathione reductase [GR] and superoxide dismutase [SOD] activities were inhibited, while malondialdehyde [MDA] level in these organs was elevated, indicative of increased lipid peroxidation. These data confirm the role of oxidative stress in radiation-induced organ toxicity and points to the possible antioxidative mechanisms of the radioprotective action of enalapril, which might be mediated by improving the balance between reactive oxygen species and antioxidant enzymes. Moreover, the beneficial effect of enalapril on serum lipid profile is suggested to be an additional mechanism of radioprotection