Induction of peroxisomal enzymes in rat liver by the hypolipidemic agent LK-903

Abstract

The effect of the hypolipidemic agent LK-903 on enzyme activities in hepatic peroxisomes of the rat was investigated. After administration of LK-903 with the chow for 14 days, the activities of hepatic catalase, urate oxidase, d-amino acid oxidase, and the fatty acyl-CoA oxidizing system were increased 2-fold, 2-fold, 2.5-fold and 7-fold, respectively. Subcellular fractionation showed that these peroxisomal enzyme activities were concentrated in the heavy mitochondrial fraction. In contrast, the peroxisomal enzyme activities of control rats were highest in the light mitochondrial fraction. During administration of LK-903, the activities of the particulate catalase, urate oxidase, and fatty acyl-CoA oxidizing system increased gradually, and reached plateau levels in about 12 days. When the rats that had received LK-903 for 14 days were subsequently given the basal diet, the particulate urate oxidase activity decreased gradually, but the activities of catalase and the fatty acyl-CoA oxidizing system remained almost unchanged for 7 days. The enhancement of catalase activity by LK-903 was due to an increase in the synthesis rate of over 2-fold; the half-life and the degradation-rate were unchanged.