Role of Angiotensin Converting Enzyme Inhibitor on the Functional Changes in Irradiated Rates

Abstract

Background: Kidney irradiation clearly leads to a progressive reduction in function associated with concomitant glomerulosclerosis and/or tubulointerstitial fibrosis. Administration of Angiotensin-converting enzyme [ACE] inhibitor markedly abrogates the severity of radiation nephropathy and can prevent the functional changes that occur after irradiation. Objective: The present study was designed to test the efficacy of converting enzyme inhibition [enalapril] and its possible mechanistic basis in preventing functional changes in irradiated rates. Method: Prior to irradiation, rats were randomized to groups receiving enalapril or no treatment, in addition to a control group of non-irradiated, non-treated rates. 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. Results: Irradiation induced significant elevations in the levels of blood urea nitrogen, serum creatinine, and serum activities of lactate dehydrogenase [LDH]; creatine kinase [CK]; alanine amino transferase [ALT]; and aspartate amino transferase [AST] compare to control values, indicative of renal, cardiac, and hepatic injury. Also there was an increase in the serum levels of triglycerides, total cholesterol, and LDL-cholesterol. On the contrary, HDL-cholesterol level was decrease. 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 injury. It can be concluded that enalapril treatment of rats prior to irradiation was able to diminish the functional changes that occur after irradiation as evidenced by a beneficial decrease in all parameters determined in the sera of these rats, with an increase in the level of HDL-cholesterol and an amelioration of inhibition of antioxidant enzymes activities in the organs of these rats.