Abstract
We investigated the protective effects of diallyl disulfide (DADS), a potent inhibitor of cytochrome P450 2E1 (CYP2E1), on ethanol-induced toxicity in human hepatocytes. We found a clear dose-dependent response between ethanol and CYP2E1 activity. The ethanol-dependent CYP2E1 enzyme activity and protein expression, lactate dehydrogenase and aspartate transaminase release, malondialdehyde formation and caspase-3 activity decreased dramatically in the presence of DADS. Furthermore, DADS increased the hepatocellular glutathione (GSH) content and prevented the ethanol-dependent cellular GSH depletion. Our data show that DADS reduces ethanol-induced toxicity in human hepatocytes by reducing CYP2E1 activity and/or stabilizing the cellular GSH content, which might be of therapeutic interest.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allyl Compounds / pharmacology*
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Aspartate Aminotransferases / metabolism
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Blotting, Western
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Caspase 3
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Caspases / metabolism
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Cytochrome P-450 CYP2E1 / metabolism
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Cytochrome P-450 CYP2E1 Inhibitors*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology*
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Ethanol / toxicity*
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Glutathione / metabolism
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Hepatocytes / drug effects
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Hepatocytes / enzymology
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Hepatocytes / metabolism
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Humans
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L-Lactate Dehydrogenase / metabolism
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Liver / drug effects*
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Liver / enzymology
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Liver / metabolism
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Malondialdehyde / metabolism
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Sulfides / pharmacology*
Substances
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Allyl Compounds
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Cytochrome P-450 CYP2E1 Inhibitors
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Enzyme Inhibitors
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Sulfides
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Ethanol
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Malondialdehyde
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allyl sulfide
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L-Lactate Dehydrogenase
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Cytochrome P-450 CYP2E1
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Aspartate Aminotransferases
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CASP3 protein, human
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Caspase 3
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Caspases
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Glutathione