PEROXISOME PROLIFERATION OF HEPATOCYTES IN RATS BY A MICROBIAL-DEGRADATION PRODUCT OF CHOLIC-ACID, 6-METHYL-3-OXO-CYCLOPENTA(F)QUINOLINE-7-YL)VALERIC ACID

Three-week oral administration of hydro-6-methyl-3-oxo-cyclopenta(f)qu inoline-7-yl)v acid (32-1328) in the diet supplemented at concentratio ns of 0.1 % or 0.3 % was associated with hepatomegaly and hypotriglyce ridemia in male F344 rats. Electron microscopic examination of the liv er revealed a remarkable increase of peroxisomes in hepatocytes both i n number and size. Biochemically, there were increased activities of p eroxisomal marker enzymes including the heat-labile enoyl-CoA hydratas e and catalase while the mitochondrial enoyl-CoA hydratase activity wa s unchanged after feeding of 32-1328. These findings indicate that 32- 1328 can exert peroxisome-proliferating activity to rat liver in a man ner similar to typical peroxisome proliferators such as clofibrate or di(2-ethylhexyl) phthalate.