title: Responses of the liver to perfluorinated fatty acids with different carbon chain length in male and female mice:in relation to induction of hepatomegaly, peroxisomal beta-oxidation and microsomal 1-acylglycerophosphocholine acyltransferase.
abstract: The potency of the induction of hepatomegaly, peroxisomal beta-oxidation and microsomal 1-acylglycerophoshocholine (1-acyl-GPC) acyltransferase was compared among perfluorinated fatty acids (PFCAs) with 6-9 carbon chain length in the liver of male and female mice. All PFCAs examined induced hepatomegaly and peroxisomal beta-oxidation and the potency was in the order of perfluorononanonic acid (PFNA), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHA) and perfluorohexanoic acid (PFHeA) when compared with the relative doses to induce the two parameters. Microsomal 1-acyl-GPC acyltransferase was induced by PFHA, PFOA and PFNA, as was peroxisomal beta-oxidation. No significant sex-related difference was observed in the induction of peroxisomal beta-oxidation by any PFCAs examined. PFNA and PFOA accumulated in the liver of both male and female mice in a dose-dependent manner. PFHA accumulated in the liver to a lesser extent; little PFHeA accumulated in the liver. Hepatic concentrations of PFNA, PFOA and PFHA were higher in male mice than those in female mice. One linear regression line was confirmed between the activities of peroxisomal beta-oxidation and hepatic concentrations of PFHeA, PFHA, PFOA and PFNA in male mice regardless of their carbon chain lengths, and the activities were saturable at the concentrations over approximately 500 nmol/g liver. Similar linear regression line was obtained between the two parameters in female mice. These results suggest (i) that the longer the perfluoroalkyl chain becomes, the more PFCA accumulates in the liver of both male and female mice, (ii) that the accumulated PFCAs induce hepatomegaly, peroxisomal beta-oxidation and microsomal 1-acyl-GPC acyltransferase, and (iii) that the difference observed in the accumulation of PFHA, PFOA and PFNA in the liver between male and female mice is not enough to produce obvious sex-related difference in the induction of peroxisomal beta-oxidation.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan. naokudo@josai.ac.jp
authors.forename: Naomi
authors.initials: N
authors.lastname: Kudo
authors.forename: Erika
authors.initials: E
authors.lastname: Suzuki-Nakajima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002208:Caproates / Q000493:pharmacokinetics / Q000633:toxicity*; D002210:Caprylates / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000493:pharmacokinetics / Q000633:toxicity*; D006529:Hepatomegaly / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism; D012727:Sex Characteristics; D013329:Structure-Activity Relationship
chemical_list: D002208:Caproates; D002210:Caprylates; D005466:Fluorocarbons; C018959:hexadecafluoro-nonanoic acid; C023036:perfluorooctanoic acid; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C479228:perfluorohexanoic acid