Catabolic Functions of Peroxisomes: Modification by Hypoupidemic Drugs

Abstract

The peroxisome is a subcellular organelle that is widely distributed in nature and which carries out both catabolic and anabolic functions (Ann. NY Acad. Sch 386:1-550, 1982). The catabolic functions include respiration (based on the formation and decomposition of H2O2) and the ß-oxidation of fatty acids. A number of drugs share the attributes of beingi) hypo-lipidemic, (2) inducers of the peroxisomal ß-oxidation enzyme system, (Lazarow, Science 197: 580-581, 1977), 3) peroxisome proliferators, and 4) carcinogens in rodents. Reddy et al. (Nature 283: 397-398, 1980) have hypothesized that peroxisome proliferators as a class may be carcinogenic Data is presented showing that bezafibrate, at a suitable hypolipidemic dose in rats, induces peroxisomal ß-oxidation but does not cause the striking organelle proliferation commonly observed with hypolipidemic drugs. Similar results have been obtained with clofibrate treatment of female rats. Christiansen et al. (Eur.). Cell Biol. 26: 77-20, 7987) have shown that feeding rats a diet rich in partially hydrogenated marine oils produces changes in the peroxisomes similar to those caused by bezafibrate. Aspirin, which is weakly hypolipidemic and a weak peroxisome proliferator, is apparently not carcinogenic in humans. The evidence indicates that the hypolipidemic effects and the peroxisome proliferative effects of these drugs are largely (although incompletely) dissociable. It suggests the need for considerable caution in evaluating the relationship, if any, between hypolipidemic and carcinogenic effects.