Peroxisome proliferation of hepatocytes in rats by a microbial degradation product of cholic acid, 4-(decahydro-6-methyl-3-oxocyclopenta(f)quinoline-7-yl)valeric acid.
Three-week oral administration of 4-(decahydro-6-methyl-3-oxo-cyclopenta(f)quinoline-7-yl)valeric acid (32-1328) in the diet supplemented at concentrations of 0.1% or 0.3% was associated with hepatomegaly and hypotriglyceridemia in male F344 rats. Electron microscopic examination of the liver revealed a remarkable increase of peroxisomes in hepatocytes both in number and size. Biochemically, there were increased activities of peroxisomal marker enzymes including the heat-labile enoyl-CoA hydratase and catalase while the mitochondrial enoyl-CoA hydratase activity was unchanged after feeding of 32-1328. These findings indicate that 32-1328 can exert peroxisome-proliferating activity to rat liver in a manner similar to typical peroxisome proliferators such as clofibrate or di(2-ethylhexyl)phthalate.
Hayashi
Y
Y
Biological Safety Research Center, National Institute of Hygienic Sciences, Tokyo, Japan.
Toyoda
K
K
Imazawa
T
T
Sato
H
H
Okamiya
H
H
Kurokawa
Y
Y
Takahashi
J
J
Mogami-Nishimaki
T
T
Hayakawa
S
S
D000818:Animals; D002478:Cells, Cultured; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014631:Valerates / Q000494:pharmacology*
D011804:Quinolines; D014631:Valerates; C083646:4-(decahydromethyl-3-oxo-1H-cyclopentaquinolinyl)valeric acid