The molecular mechanisms of diallyl disulfide and diallyl sulfide induced hepatocyte cytotoxicity |
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Authors: | D. Truong |
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Affiliation: | Graduate Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, Ontario, Canada M5S 3M2 |
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Abstract: | Diallyl disulfide (DADS) and diallyl sulfide (DAS) are the major metabolites found in garlic oil and have been reported to lower cholesterol and prevent cancer. The molecular cytotoxic mechanisms of DADS and DAS have not been determined.The cytotoxic effectiveness of hydrogen versus allyl sulfides towards hepatocytes was found to be as follows: NaHS > DADS > DAS. Hepatocyte mitochondrial membrane potential was decreased and reactive oxygen species (ROS) and TBARS formation was increased by all three allyl sulfides. (1) DADS induced cytotoxicity was prevented by the H2S scavenger hydroxocobalamin, which also prevented cytochrome oxidase dependent mitochondrial respiration suggesting that H2S inhibition of cytochrome oxidase contributed to DADS hepatocyte cytotoxicity. (2) DAS cytotoxicity on the other hand was prevented by hydralazine, an acrolein trap. Hydralazine also prevented DAS induced GSH depletion, decreased mitochondrial membrane potential and increased ROS and TBARS formation. Chloral hydrate, the aldehyde dehydrogenase 2 inhibitor, however had the opposite effects, which could suggest that acrolein contributed to DAS hepatocyte cytotoxicity. |
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Keywords: | DADS, diallyl disulfide DAS, diallyl sulfide NaHS, sodium hydrosulfide H2S, hydrogen sulfide PM, propyl mercaptan AM, allyl mercaptan AMS, allyl methyl sulfide AMSO, allyl methyl sulfoxide AMSO2, allyl methyl sulfone DASO, diallyl sulfone DASO2, diallyl sulfoxide ROS, reactive oxygen species TBARS, thiobarbituric acid reactive species ALDH2, aldehyde dehydrogenase 2 DTT, dithiothreitol GST, glutathione-s-transferase |
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