Deficiency in Cytosolic Malic Enzyme Does Not Increase Acetaminophen-Induced Hepato-Toxicity
| Autor: | Michael R. Tota, Su Qian, Peter Nizner, Sheena Mumick, Joseph Menetski, Marc L. Reitman, Douglas J. MacNeil |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Genotype Glutathione reductase Malic enzyme Biology Toxicology Malate dehydrogenase Mice chemistry.chemical_compound Cytosol Malate Dehydrogenase Internal medicine medicine Animals Glycolysis Acetaminophen Pharmacology Liver injury Analgesics General Medicine Glutathione medicine.disease Mice Mutant Strains Mice Inbred C57BL Citric acid cycle Endocrinology Liver Biochemistry chemistry Chemical and Drug Induced Liver Injury NADP Nicotinamide adenine dinucleotide phosphate |
| Zdroj: | Basic & Clinical Pharmacology & Toxicology. 103:36-42 |
| ISSN: | 1742-7843 1742-7835 |
| DOI: | 10.1111/j.1742-7843.2008.00228.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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