title: Assessment of urinary metabolite excretion after rat acute exposure to perfluorooctanoic acid and other peroxisomal proliferators.
abstract: Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant. Activation of the peroxisome proliferator activated receptor alpha (PPARα) resulting from exposure to PFOA has been extensively studied in rodents. However, marked differences in response to peroxisome proliferators prevent extrapolation of rodent PPARα activation to human health risks and additional molecular mechanisms may also be involved in the biological response to PFOA exposure. To further explore the potential involvement of such additional pathways, the effects of PFOA exposure on urinary metabolites were directly compared with those of other well-known PPARα agonists. Male rats were administered PFOA (10, 33, or 100 mg/kg/d), fenofibrate (100 mg/kg/d), or di(2-ethylhexyl) phthalate (100 mg/kg/d) by gavage for 3 consecutive days and allowed to recover for 4 days, and overnight urine was collected. Greater urinary output was observed exclusively in PFOA-treated rats as the total fraction of PFOA excreted in urine increased with the dose administered. Assessment of urinary metabolites (ascorbic acid, quinolinic acid, 8-hydroxy-2'-deoxyguanosine, and malondialdehyde) provided additional information on PFOA's effects on hepatic glucuronic acid and tryptophan-nicotinamide adenine dinucleotide (NAD) pathways and on oxidative stress, whereas increased liver weight and palmitoyl-CoA oxidase activity indicative of PPARα activation and peroxisomal proliferation persisted up to day five after the last exposure.
authors.forename: Marc
authors.initials: M
authors.lastname: Rigden
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pelletier
authors.forename: Raymond
authors.initials: R
authors.lastname: Poon
authors.forename: Jiping
authors.initials: J
authors.lastname: Zhu
authors.forename: Christiane
authors.initials: C
authors.lastname: Auray-Blais
authors.forename: René
authors.initials: R
authors.lastname: Gagnon
authors.forename: Cariton
authors.initials: C
authors.lastname: Kubwabo
authors.forename: Ivana
authors.initials: I
authors.lastname: Kosarac
authors.forename: Kaela
authors.initials: K
authors.lastname: Lalonde
authors.forename: Sabit
authors.initials: S
authors.lastname: Cakmak
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
authors.forename: Karen
authors.initials: K
authors.lastname: Leingartner
authors.forename: Ka Lei
authors.initials: KL
authors.lastname: Ku
authors.forename: Ranjan
authors.initials: R
authors.lastname: Bose
authors.forename: Jianli
authors.initials: J
authors.lastname: Jiao
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002210:Caprylates / Q000633:toxicity* / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D005466:Fluorocarbons / Q000633:toxicity* / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D020025:Peroxisome Proliferators / Q000633:toxicity* / Q000652:urine; D051381:Rats
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; D020025:Peroxisome Proliferators; D000080242:8-Hydroxy-2'-Deoxyguanosine; C023036:perfluorooctanoic acid; D003849:Deoxyguanosine