Journal article
Effects of thiol antioxidants on the atropselective oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) by rat liver microsomes
Environmental science and pollution research international, Vol.23(3), pp.2081-2088
02/2016
DOI: 10.1007/s11356-015-4987-4
PMCID: PMC4706823
PMID: 26155892
Abstract
Chiral polychlorinated biphenyl (PCB) congeners, such as PCB 136, are atropselectively metabolized to various hydroxylated PCB metabolites (HO-PCBs). The present study investigates the effect of two thiol antioxidants, glutathione and N-acetyl-cysteine (NAC), on profiles and chiral signatures of PCB 136 and its HO-PCB metabolites in rat liver microsomal incubations. Liver microsomes prepared from rats pretreated with phenobarbital were incubated with PCB 136 (5 μM) in the presence of the respective antioxidant (0-10 mM), and levels and chiral signatures of PCB 136 and its HO-PCB metabolites were determined. Three metabolites, 5-136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol), 4-136 (2,2',3,3',6,6'-hexachlorobiphenyl-4-ol), and 4,5-136 (2,2',3,3',6,6'-hexachlorobiphenyl-4,5-diol), were detected in all incubations, with 5-136 being the major metabolite. Compared to microsomal incubations without antioxidant, levels of 4,5-136 increased with increasing antioxidant concentration, whereas levels of PCB 136 and both mono-HO-PCBs were not affected by the presence of either antioxidant. PCB 136, 4-136, and 5-136 displayed significant atropisomeric enrichment; however, the direction and extent of the atropisomeric enrichment was not altered in the presence of an antioxidant. Because 4,5-136 can either be conjugated to a sulfate or glucuronide metabolite that is readily excreted or further oxidized a potentially toxic PCB 136 quinone, the effect of both thiol antioxidants on 4,5-136 formation suggests that disruptions of glutathione homeostasis may alter the balance between both metabolic pathways and, thus, PCB 136 toxicity in vivo.
Details
- Title: Subtitle
- Effects of thiol antioxidants on the atropselective oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) by rat liver microsomes
- Creators
- Xianai Wu - University of IowaHans-Joachim Lehmler - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Environmental science and pollution research international, Vol.23(3), pp.2081-2088
- DOI
- 10.1007/s11356-015-4987-4
- PMID
- 26155892
- PMCID
- PMC4706823
- ISSN
- 0944-1344
- eISSN
- 1614-7499
- Grant note
- ES06694 / NIEHS NIH HHS P30 ES005605 / NIEHS NIH HHS R01 ES017425 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS ES017425 / NIEHS NIH HHS P30 ES006694 / NIEHS NIH HHS ES05605 / NIEHS NIH HHS R01 ES014901 / NIEHS NIH HHS ES013661 / NIEHS NIH HHS
- Language
- English
- Date published
- 02/2016
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984285611702771
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