Long-term cell culture models for the analysis of hepatotoxicity in vitro

Tuschl, Gregor; Hrach, Jens; Richert, Lysiane; Chesné, Christophe; Hewitt, Philip; Mueller, Stefan O.

doi:10.1016/j.toxlet.2007.05.267

Cited by 1 publication

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“…Hepatocytes in suspension preserve most drug metabolizing enzymes at in vivo levels for several hours. However, their lack of cell–cell and cell–matrix contact limits their use to incubation times of 3 h, where the hepatocyte viability is still maintained at >80% (Tuschl et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites in rat hepatocytes

Chan

Lehmler

Sivagnanam

et al. 2009

J of Applied Toxicology

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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.

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Section: Discussionmentioning

confidence: 99%