Characterization of hepatic responses of rat to administration of perfluorooctanoic and perfluorodecanoic acids at low levels.
Male rats were fed a diet that contained perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) at concentrations ranging from 0.0025-0.04% (w/w) and from 0.00125-0.01% (w/w), respectively, for 1 week. The hepatic responses of the rats to PFOA and PFDA were examined. Upon the administration of PFOA and PFDA, three peroxisome proliferator-responsive parameters, peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase and cytosolic long-chain acyl-CoA hydrolase, were induced in a dose-dependent manner. A multiple regression analysis of the three parameters revealed that the data from rats treated with PFOA and PFDA shared one common line, indicating a marked correlation among the inductions of the three parameters. The activities of glutathione (GSH) S-transferases towards 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB) were depressed by PFOA and PFDA. Significant inverse correlations were found between activities of GSH S-transferases and peroxisomal beta-oxidation. The administration of PFOA and PFDA significantly increased hepatic concentration of triacylglycerol. The perfluorocarboxylic acids at relatively high doses caused accumulation of cholesterol in liver. Electron microscopic studies showed that the administration of PFOA and PFDA caused an increase in cell size and proliferations of peroxisomes, and that the treatment of rats with PFDA at dietary concentration of 0.01% caused a marked increase in small lipid droplet in hepatocytes, indicative of hepatotoxic manifestations. The present results suggest that when PFOA and PFDA are administered at low levels, there are no differences between the properties of the perfluorocarboxylic acids as peroxisome proliferators, although the administration of PFDA at the doses exceeding a certain level becomes markedly toxic to hepatocytes.
Kawashima
Y
Y
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Kobayashi
H
H
Miura
H
H
Kozuka
H
H
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000008:administration & dosage / Q000633:toxicity*; D003652:Decanoic Acids / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D002210:Caprylates; D003652:Decanoic Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid; C023036:perfluorooctanoic acid