Protective effects of anethole dithiolethione against oxidative stress-induced cytotoxicity in human Jurkat T cells.
The protective effects of anethole dithiolethione (ADT) against H2O2- or 4-hydroxynonenal (HNE)-induced cytotoxicity in human Jurkat T cells were investigated. Jurkat T cells were pretreated with ADT (10-50 microM) for 18 hr and then challenged with H202 or HNE for up to 4 hr. Cytotoxicity was assessed by measuring: 1) leakage of lactate dehydrogenase from cells to medium; and 2) exclusion of the DNA intercalating fluorescent probe propidium iodide by viable cells. Pretreatment of cells with ADT (10 or 25 microM) for 18 hr significantly protected cells against H202- or HNE-induced cytotoxicity. Treatment of cells with ADT (10-50 microM) for 72 hr significantly increased the activities of catalase and glutathione reductase. The maximum effect of ADT treatment on the activity of these enzymes was observed when cells were treated with 25 microM of ADT for 72 hr. A significant increase in cellular GSH was observed in cells that were treated with ADT for 72 hr. Using monobromobimane as a thiol probe, we consistently observed that cells pretreated for 18 hr with ADT (25 or 50 microM) had also increased total thiol content. Exposure of Jurkat T cells to H202 or HNE resulted in a time-dependent decrease in cellular GSH. ADT (10-50 microM, 18 hr) pretreatment circumvented H202-dependent lowering of cellular GSH. In conclusion, ADT proved to be a potent cytoprotective thiol antioxidant with multifaceted mechanisms of action, suggesting that the drug has a remarkable therapeutic potential.
Khanna
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Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Sen
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Roy
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Christen
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Packer
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D000781:Anethole Trithione / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D004563:Electrochemistry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D007700:Kinetics; D019272:Leukocyte Elastase / Q000378:metabolism; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000378:metabolism
D003470:Culture Media; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D019272:Leukocyte Elastase; D005978:Glutathione; D000781:Anethole Trithione