Decrease of superoxide dismutase and glutathione peroxidase in liver of rats treated with hypolipidemic drugs

Abstract

1. INTRODUCTION Clofibrate and other hypolipidemic drugs in- crease the number of hepatic peroxisomes and cause a corresponding increase of several peroxi- somal enzyme activities [ 1,2]. This effect regards HlOz-generating reactions (most typically, palmi- toyl-CoA oxidase activity) and catalase, which is able to destroy most of the Hz02 formed within the organelle. It is reasonable to expect that the net flux of Hz02 outside the organelle should be enhanced under hypolipidemic treatment in view of the fact that significant Hz02 diffusion is observed in per- oxisomes of untreated animals [3,4] and the increase of palmitoyl-CoA oxidase activity induced by clo- tibrate feeding is much higher than that of catalase [ 11. Moreover, hypolipidemic agents cause prolif- eration of hepatic smooth endoplasmic reticulum as well, and this produces a marked increase of cyto- chrome P450 [5], which is likely to be a major source of Ozand H202 in the cell as suggested by results obtained with subcellular preparations [6,7]. It seemed therefore interesting to investigate whether activities of cytoplasmic enzymes acting as a defense against ‘oxygen radicals’ (i.e., superoxide dis- mutase and glutathione peroxidase) are affected by feeding hypolipidemic drugs. The results reported here show that both enzymes are significantly de- creased in rat liver during treatment with clofibrate and procetofene, another hypolipidemic agent [S]. This effect is associated with an increased suscepti- bility of the tissue to enhanced peroxidative risk, as *