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Assessment of Urinary Metabolite Excretion After Rat Acute Exposure to Perfluorooctanoic Acid and Other Peroxisomal Proliferators

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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.

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Acknowledgments

This project was funded through Health Canada A-Base. The authors thank Brita Nadeau for excellent technical assistance and Mike Wade and Premkumari Kumarathasan for helpful comments on the manuscript.

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Authors and Affiliations

  1. Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, K1A 0L2, Canada

    Marc Rigden, Guillaume Pelletier, Raymond Poon, Jiping Zhu, Cariton Kubwabo, Ivana Kosarac, Kaela Lalonde, Sabit Cakmak, Bin Xiao, Karen Leingartner & Ka Lei Ku

  2. Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada

    Christiane Auray-Blais & René Gagnon

  3. New Substances Assessment and Control Bureau, Health Canada, Ottawa, ON, K1A 0K9, Canada

    Ranjan Bose & Jianli Jiao

  4. Environmental Health Centre, 50 Colombine Driveway, P.L. 0803B Tunney’s Pasture, Ottawa, ON, K1A 0L2, Canada

    Guillaume Pelletier

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  1. Marc Rigden
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Rigden, M., Pelletier, G., Poon, R. et al. Assessment of Urinary Metabolite Excretion After Rat Acute Exposure to Perfluorooctanoic Acid and Other Peroxisomal Proliferators. Arch Environ Contam Toxicol 68, 148–158 (2015). https://doi.org/10.1007/s00244-014-0058-y

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