title: Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process-affected water: evidence for inhibition of P-glycoprotein.
abstract: Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada.
authors: Hattan A
authors: HA
authors: Alharbi
authors: Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada.|College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.
authors: Jane
authors: J
authors: Alcorn
authors: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.
authors: Ahmed
authors: A
authors: Al-Mousa
authors: Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada.|Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, Canada.|Zoology Department, Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.|School of Biological Sciences, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
authors: John P
authors: JP
authors: Giesy
authors: Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada.
authors: Steve B
authors: SB
authors: Wiseman
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000416:Alberta; D000818:Animals; D001822:Body Burden; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004390:Chlorpyrifos / Q000493:pharmacokinetics / Q000633:toxicity*; D004625:Embryo, Nonmammalian; D005618:Fresh Water; D006207:Half-Life; D006801:Humans; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D007814:Larva; D008294:Malathion / Q000633:toxicity; D061329:Oil and Gas Fields; D009990:Oryzias / Q000378:metabolism / Q000502:physiology*; D016019:Survival Analysis; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007306:Insecticides; D014874:Water Pollutants, Chemical; D004390:Chlorpyrifos; D008294:Malathion
keywords: ABC protein; Bitumen; chemosensitization; chlorpyrifos; naphthenic acid; tailings ponds