Cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites in rat hepatocytes

Katie Chan; Hans-Joachim Lehmler; Milani Sivagnanam; Cynthia Yan Feng; Larry Robertson; Peter J O’Brien

doi:10.1002/jat.1483

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Cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites in rat hepatocytes

Journal article

Open access

Peer reviewed

Cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites in rat hepatocytes

Katie Chan, Hans-Joachim Lehmler, Milani Sivagnanam, Cynthia Yan Feng, Larry Robertson and Peter J O’Brien

Journal of applied toxicology, Vol.30(2), pp.163-171

03/2010

DOI: 10.1002/jat.1483

PMCID: PMC6658179

PMID: 19830680

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https://www.ncbi.nlm.nih.gov/pmc/articles/6658179View

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Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that exhibit various toxic effects in animals and exposed human populations. The molecular mechanisms of PCB toxicity have been attributed to the toxicological properties of its metabolites, such as hydroquinones, formed by cytochrome-P-450 oxidation. The effects of PCB hydroquinone metabolites towards freshly isolated rat hepatocytes were investigated. Hydroquinones can be oxidized to semiquinones and/or quinone metabolites. These metabolites can conjugate glutathione or can oxidize glutathione as a result of redox cycling. This depletes hepatocyte glutathione, which can inhibit cellular defence mechanisms, causing cell death and an increased susceptibility to oxidative stress. However in the following, glutathione-depleted hepatocytes became more resistant to the hydroquinone metabolites of PCBs. This suggested that their glutathione conjugates were toxic and that there was a third type of quinone toxicity mechanism which involved a hydrogen peroxide-accelerated autoxidation of the hydroquinones to form toxic electrophilic quinone and semiquinone-glutathione conjugates.

polychlorinated biphenyls

mitochondria

glutathione

2-(x′-chlorophenyl)-1,4-hydroquinone

hepatocytes

oxidative stress

hydroquinone

Details

Title: Subtitle: Cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites in rat hepatocytes
Creators: Katie Chan - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA
Milani Sivagnanam - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA
Cynthia Yan Feng - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA
Larry Robertson - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA
Peter J O’Brien - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Journal of applied toxicology, Vol.30(2), pp.163-171
DOI: 10.1002/jat.1483
PMID: 19830680
PMCID: PMC6658179
NLM abbreviation: J Appl Toxicol
ISSN: 0260-437X
eISSN: 1099-1263
Language: English
Date published: 03/2010
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984000932002771

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