Irreversible inhibition of hepatic glutathione S-transferase by ciprofibrate, a peroxisome proliferator

Abstract

Ciprofibrate (2-[4-(2,2-dichlorocyclopropyl) phenoxy]2-methyl propionic acid) which is a hypolipidemic agent and has been shown to cause peroxisome proliferation, non-competitively inhibits glutathione S-transferase activity of rat liver, both in vivo and in vitro. Among all the glutathione S-transferases of rat liver, ligandin is maximally inhibited by ciprofibrate. Studies with the purified glutathione S-transferases of rat liver indicate that the affinities of different subunits of liver enzymes for ciprofibrate are in the order Ya greater than Yb, Yb' greater than Yc.