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Am J Physiol Gastrointest Liver Physiol 281: G1135-G1139, 2001;
0193-1857/01 $5.00
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Vol. 281, Issue 5, G1135-G1139, November 2001

THEME
Nonalcoholic Steatosis and Steatohepatitis
II. Cytochrome P-450 enzymes and oxidative stress

Graham Robertson, Isabelle Leclercq, and Geoffrey C. Farrell

Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, New South Wales 2145, Australia

Oxidative stress is present in the liver of humans with steatosis and nonalcoholic steatohepatitis (NASH) and is a plausible mediator of cellular injury, inflammatory recruitment, and fibrogenesis. CYPs 2E1 and 4A are the microsomal oxidases involved with fatty acid oxidation. Both enzymes can reduce molecular oxygen to produce prooxidant species, which, if not countered efficiently by antioxidants, create oxidative stress. In this theme article, we present the evidence that, in the context of hepatic steatosis, CYPs 2E1 and 4A could generate the "second hit" of cellular injury, particularly when antioxidant reserves are depleted, and propose ways in which this could contribute to the pathogenesis of NASH.

nonalcoholic steatohepatitis; CYP2E1; CYP4A; microsomal lipid peroxidation; antioxidants


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