Role of free radicals in the pathogenesis of lipid-induced glomerulosclerosis in rats

Background. We examined whether a high-cholesterol (HC) diet causes glomeru losclerosis in rats, and investigated the role of free radicals and lipid p eroxidation in lipid-induced glomerulosclerosis. Methods. The rats were given a normal diet, a HC diet, or a HC diet with an tioxidants and radical scavengers. Serum levels of lipid, lipid peroxide (L OOH), urinary excretion of protein (UP), and urinary norepinephrine excreti on (UNE) were measured. The glomerular sclerosing score was used to evaluat e the renal injury. Results. Blood pressure, total cholesterol, and LOOH were increased by a HC diet, as were UP and UNE. The HC diet induced renal injury. Treatment with superoxide dismutase, dimetylthiourea as a scavenger of hydroxyl radical ( OH .), def-feroxamine masilate as an iron chelator, or vitamin E inhibited the increases in blood pressure, LOOH, UP, and UNE, whereas total cholester ol was not affected. The production of superoxide anion (O-2(-).) by neutro phil and LOOH in the kidney was increased, and superoxide dismutase and hyd rogen peroxide in the kidney were decreased. Almost all of these changes we re attenuated by vitamin E; however, the O-2(-). production was not inhibit ed. OH . was increased by the HC diet, and it was normalized with the treat ments. Furthermore, the sclerosing score was partially suppressed by the tr eatments. Ferric iron was stained in the proximal tubulus, and it was not o bserved in the treated rats. Conclusions. The data suggest that lipid peroxidation is involved in the pa thogenesis of lipid induced glomerulosclerosis and that O-2(-). and OH . ma y play a role in the process.