Short and long term influence of phenothiazines on liver peroxisomal fatty acid oxidation in rodents

Evidence is given that phenothiazines depress hepatic peroxisomal fatty acid oxidation in vivo. After oral administration to rats thioridazine and chlorpromazine inhibit peroxisomal beta-oxidation, evaluated by H2O2 production, during 2 weeks. In mice, this effect could not be demonstrated. However, in both species VLCFA are increased after short and long term drug administration. Electron microscopy reveals the presence of membranous structures in liver cytoplasm or lysosomes. The inhibition by thioridazine of peroxisomal beta-oxidation does not lead to hepatic peroxisome proliferation. The activities of enzymes related to fatty acid breakdown are not increased and liver peroxisomes are microscopically normal.