Hydrogen peroxide-induced glutathione depletion and aldehyde dehydrogenase inhibition in erythrocytes.
To study relationships between lipid peroxidation and aldehyde dehydrogenase (ALDH) inhibition, the Stocks and Dormandy model of H2O2-induced lipid peroxidation in erythrocytes was employed. Hydrogen peroxide treatment of erythrocytes and erythrocyte lysates caused a dose-dependent inhibition and depletion of ALDH and reduced glutathione (GSH) respectively. Complete ALDH inhibition and glutathione depletion occurred before significant lipid peroxidation was detected by HPLC analysis of malondialdehyde-thiobarbituric acid adducts. Hydroxyl radical scavengers did not antagonize the hydrogen peroxide-induced enzyme inhibition. Studies with the iron chelator desferrioxamine suggested that the hydrogen peroxide-induced ALDH inhibition was mediated by iron in erythrocyte lysates but not in semi-purified (and Chelex-treated) ALDH preparations. Glutathione peroxidase reduction of H2O2 exhibited an anomalous GSH dependence which was not in agreement with the accepted reaction mechanism. Reduced glutathione also antagonized the hydrogen peroxide-induced ALDH inhibition by possible complex formation with the enzyme. A hypothetical model is presented which accounts for the observed responses to hydrogen peroxide.
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000097:blood; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000097:blood* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006878:Hydroxides / Q000097:blood; D017665:Hydroxyl Radical; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010084:Oxidation-Reduction; D011817:Rabbits
D006878:Hydroxides; D008054:Lipid Peroxides; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D002374:Catalase; D000444:Aldehyde Dehydrogenase; D005978:Glutathione; D003676:Deferoxamine