Characterization of arsenic hepatobiliary transport using sandwich-cultured human hepatocytes

Toxicological Sciences : an Official Journal of the Society of Toxicology
Barbara A RoggenbeckElaine M Leslie

Abstract

Arsenic is a proven human carcinogen and is associated with a myriad of other adverse health effects. This metalloid is methylated in human liver to monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)), dimethylarsinic acid (DMA(V)), and dimethylarsinous acid (DMA(III)) and eliminated predominantly in urine. Hepatic basolateral transport of arsenic species is ultimately critical for urinary elimination; however, these pathways are not fully elucidated in humans. A potentially important human hepatic basolateral transporter is the ATP-binding cassette (ABC) transporter multidrug resistance protein 4 (MRP4/ABCC4) that in vitro is a high-affinity transporter of DMA(V) and the diglutathione conjugate of MMA(III) [MMA(GS)(2)]. In rats, the related canalicular transporter Mrp2/Abcc2 is required for biliary excretion of arsenic as As(GS)(3) and MMA(GS)(2). The current study used sandwich cultured human hepatocytes (SCHH) as a physiological model of human arsenic hepatobiliary transport. Arsenic efflux was detected only across the basolateral membrane for 9 out of 14 SCHH preparations, 5 had both basolateral and canalicular efflux. Basolateral transport of arsenic was temperature- and GSH-dependent and inhibited by the M...Continue Reading

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Citations

Feb 13, 2016·Journal of Pharmaceutical Sciences·Kyunghee YangKim L R Brouwer
May 13, 2017·International Journal of Molecular Sciences·Sarah E Orr, Christy C Bridges
Sep 1, 2018·European Journal of Drug Metabolism and Pharmacokinetics·Olivier FardelYannick Parmentier
Nov 1, 2020·Reviews on Environmental Health·Tahereh FarkhondehAli Naghizadeh
Dec 28, 2017·Environmental Science & Technology·Qingqing LiuX Chris Le

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