PYRUVATE INHIBITS CLOFIBRATE-INDUCED HEPATIC PEROXISOMAL PROLIFERATION AND FREE-RADICAL PRODUCTION IN RATS

In an effort to identity the effects of the 3-carbon compound pyruvate on free radical production, we measured hepatic total peroxisomal B-o xidation and catalase activity and the production of lipofuscin-like p roducts in male Sprague-Dawley rats consuming an adequate diet supplem ented with pyruvate, vitamin E, or the peroxisome proliferator and fre e radical enhancer clofibrate for 22 days (n = 5 in each group). Clofi brate feeding induced hepatomegaly, a fivefold increase in total perox isomal p-oxidation activity, and a threefold increase in hepatic lipof uscin-like products (P < .05). Pyruvate but not vitamin E inhibited th e increase in liver size by 70% (P < .05). Both pyruvate and Vitamin E completely inhibited clofibrate-induced increases in lipofuscin-like products (P < .05). Pyruvate but not clofibrate or vitamin E increased plasma concentrations of the nitric oxide metabolites nitrite and nit rate (P < .05). We conclude that with clofibrate-induced peroxisomal p roliferation and free radical production, pyruvate will inhibit peroxi somal proliferation and free radical production, inhibit free radical- induced lipid peroxidation, and enhance metabolism of nitric oxide. Co pyright (C) 1995 by W.B. Saunders Company