The effects of hypolipidemic agents derived from procetofenic acid on the activity of superoxide dismutase and glutathione peroxidase and on malonyl dialdehyde production of rat liver.

Male and female rats were treated with hypolipidemic agents derived from procetofenic acid, namely fenofibrate ( procetofene ), cholestyrammonium alpha-(4-p-chlorobenzoyl-phenoxy)-isobutyrate (Alfa-1081) and alpha-(4-p-chlorobenzoyl-phenoxy)-isobutyryl-taurine (35/ipo). A marked decrease of liver superoxide dismutase and glutathione peroxidase was observed in the male rats treated with fenofibrate. In this sample a significant increase of malonyl dialdehyde was also detected when the liver homogenates were subjected to a test of lipid peroxidation induced by active oxygen species. Alfa-1081 and 35/ipo produced no substantial changes of superoxide dismutase and glutathione peroxidase and no significant increase of peroxidation products. These results, while providing an in vivo evidence for the role of superoxide dismutase and glutathione peroxidase as antioxidant enzymes, indicate that hypolipidemic agents can affect also enzymes not bound to membranes as they do with peroxisomal enzymes. The side effect presented here may be harmful, since it can lead to an augmented risk of lipid peroxidation in tissues. It is, however, clear that also within the same class of hypolipidemic drugs the effect is not always present. Peroxidative damage should therefore be considered as a key parameter in the characterization of hypolipidemic agents.