Effects of prolonged administration of perfluorooctanoic acid on hepatic activities of enzymes which detoxify peroxide and xenobiotic in the rat.
Male and female rats were fed a diet containing 0.01% (w/w) perfluorooctanoic acid (PFOA) for 2 or 26 weeks, and the effects on enzymes that participate in the metabolism of peroxides and xenobiotics in liver were studied. Elevated activity of peroxisomal beta-oxidation persisted throughout the treatment of male rats with PFOA for 26 weeks. The activity of glutathione (GSH) peroxidase towards hydrogen peroxide was depressed significantly by the prolonged administration. The long-term treatment of male rats with PFOA decreased the activity of GSH peroxidase towards cumene hydroperoxide and increased the activity of microsomal NADPH-dependent lipid peroxidation. The activities of GSH reductase and hepatic content of GSH remained unchanged. There was no difference in the content of conjugated dienes in microsomal lipid between male rats exposed to PFOA for 26 weeks and age-matched control. The activities of GSH S-transferase towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene were depressed by the short-term administration of PFOA to male rats, and this inhibition became pronounced during the prolonged treatment. Microsomal cytochrome P450 was induced by the short-term treatment of male rats with PFOA, and elevated levels persisted throughout the treatment for 26 weeks. Upon the administration of PFOA to male rats for 2 weeks, the activity of 7-ethoxycoumarin O-deethylase was increased markedly, whereas the activities of either aniline p-hydroxylase or aminopyrine N-demethylase were unchanged. Although an age-dependent decrease was observed in the activity of 7-ethoxycoumarin O-deethylase, the activity in male rats treated with PFOA for 26 weeks was higher than that of age-matched control, to the same extent as was observed with the short-term treatment. The prolonged administration of PFOA to male rats caused a significant increase in the activity of both aniline p-hydroxylase and aminopyrine N-demethylase. Little changes were found in the same parameters tested in female rats even after the prolonged administration of PFOA.
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Y
Y
Kawashima
S
S
Suzuki
H
H
Kozuka
M
M
Sato
Y
Y
Suzuki
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008658:Inactivation, Metabolic; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D015262:Xenobiotics / Q000378:metabolism*
D002210:Caprylates; D005466:Fluorocarbons; D015262:Xenobiotics; C023036:perfluorooctanoic acid; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase