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Updated: Jul 6, 2026

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Deficiency in cytosolic malic enzyme does not increase acetaminophen-induced hepato-toxicity
Su Qian1, Sheena Mumick, Peter Nizner
1Department of Metabolic Disorders, Merck Research Laboratories, Rahway, NJ, USA. su_qian@merck.com
Abstract:
Cytosolic malic enzyme (ME-1) is a nicotinamide adenine dinucleotide phosphate (NADP)-dependent enzyme that generates NADPH. The activity of this enzyme, the reversible oxidative decarboxylation of malate to yield pyruvate, links glycolytic pathway to citric acid cycle. The high level of ME-1 expression in liver, and its involvement in NADPH production, suggests reduced ME-1 activity might compromise hepatic production of reduced glutathione (GSH) by the NADPH-dependent enzyme glutathione reductase, and hence affect xenobiotic detoxification. The role of ME-1 in liver detoxification was evaluated in Mod1 deficient mice (mod1(-/-)) by evaluating their sensitivity to acetaminophen-induced liver injury. The results show that mod1(-/-) mice are not more sensitive to acetaminophen hepato-toxicity. Although GSH levels were initially depleted more in the mod1(-/-) liver than in wild-type controls, the GSH levels recovered quickly. In conclusion, our data indicate that ME-1 deficiency does not adversely affect GSH-dependent detoxification.
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