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

Background. We examined whether a high-cholesterol (HC) diet causes glomerulosclerosis in rats, and investigated the role of free radicals and lipid peroxidation in lipid-induced glomerulosclerosis. Methods. The rats were given a normal diet, a HC diet, or a HC diet with antioxidants and radical scavengers. Serum levels of lipid, lipid peroxide (LOOH), urinary excretion of protein (UP), and urinary norepinephrine excretion (UNE) were measured. The glomerular sclerosing score was used to evaluate 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 cholesterol was not affected. The production of superoxide anion (O-2(-).) by neutrophil and LOOH in the kidney was increased, and superoxide dismutase and hydrogen peroxide in the kidney were decreased. Almost all of these changes were attenuated by vitamin E; however, the O-2(-). production was not inhibited. OH . was increased by the HC diet, and it was normalized with the treatments. Furthermore, the sclerosing score was partially suppressed by the treatments. Ferric iron was stained in the proximal tubulus, and it was not observed in the treated rats. Conclusions. The data suggest that lipid peroxidation is involved in the pathogenesis of lipid induced glomerulosclerosis and that O-2(-). and OH . may play a role in the process.