Molecular mechanisms underlying chemical liver injury

Xinsheng Gu; Jose E. Manautou

doi:10.1017/S1462399411002110

Molecular mechanisms underlying chemical liver injury

Published online by Cambridge University Press: 03 February 2012

Xinsheng Gu and

Jose E. Manautou

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Xinsheng Gu: Affiliation:
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA
Jose E. Manautou*: Affiliation:
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA
*: *Corresponding author: Jose E. Manautou, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269, USA. E-mail: jose.manautou@uconn.edu

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Abstract

The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 14 , March 2012 , e4

DOI: https://doi.org/10.1017/S1462399411002110 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2012

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Molecular mechanisms underlying chemical liver injury

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Molecular mechanisms underlying chemical liver injury

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