Effect of clofibrate on lipid peroxidation in rats treated with aspirin and 4-pentenoic acid.

The in vivo hepatic lipid peroxide content of rats was increased by aspirin or 4-pentenoic acid (4-PA) administration but was decreased by clofibrate (CPIB) administration. The increase by aspirin or 4-PA treatment was depressed by simultaneous administration of CPIB. However, the in vitro formation of lipid peroxide in liver mitochondria and microsomes of rats treated with CPIB as well as aspirin and 4-PA was also elevated compared to that of control rats. The formation of lipid peroxide in mitochondria and microsomes of control rats in vitro was depressed by the addition of cytosols obtained from untreated (control), aspirin-treated, 4-PA-treated, and CPIB-treated rats, but was not depressed by the addition of albumin or heated cytosols. The most effective depression was obtained by the addition of cytosol obtained from CPIB-treated rats. In addition, glutathione peroxidase activity and nonprotein sulfhydryl content in cytosol obtained from CPIB-treated rats were elevated compared to those from control, aspirin, and 4-PA-treated rats. The results suggest that the action of CPIB may be mainly related to the increase of cytosolic glutathione peroxidase activity and nonprotein sulfhydryl content. Hepatic triglyceride and phospholipid contents of rats treated with aspirin or 4-PA were increased compared to those of control rats. These increases were also reversed by simultaneous administration of CPIB.