Captopril scavenges hydrogen peroxide and reduces, but does not eliminate, oxidant-induced cell injury.
We investigated whether captopril, an angiotensin-converting enzyme (ACE) inhibitor with a sulfhydryl group, enalaprilat, an ACE inhibitor without a sulfhydryl group, and cysteine, an amino acid with a sulfhydryl group but no ACE-inhibiting properties, could scavenge hydrogen peroxide and prevent oxidant-induced cell injury. When 0.1-2.5 mM concentrations of captopril, cysteine, or enalaprilat were incubated with xanthine oxidase and hypoxanthine for 0-120 min, the recovery of hydrogen peroxide was significantly (P < 0.001) reduced in the presence of captopril or cysteine, whereas enalaprilat had no effect on the recovery of hydrogen peroxide. Captopril and cysteine could not scavenge hydrogen peroxide when the sulfhydryl group was blocked with N-ethylmaleimide. When human renal tubular epithelial cells and human umbilical vein endothelial cells were exposed to hydrogen peroxide, oxidant-induced depletion of ATP and efflux of [3H]adenine metabolites was mildly reduced in the presence of captopril or cysteine but was not altered by enalaprilat. Cysteine was more effective in preventing oxidant-induced cell injury than captopril. We conclude that because of its sulfhydryl group, captopril at millimolar concentrations can scavenge hydrogen peroxide and can slightly reduce, but does not eliminate, oxidant-induced cell injury.
Andreoli
S P
SP
Department of Pediatrics, Indiana University Medical Center, Indianapolis 46223.
D002216:Captopril / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016166:Free Radical Scavengers; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects
D016166:Free Radical Scavengers; D016877:Oxidants; D002216:Captopril; D006861:Hydrogen Peroxide; D005978:Glutathione; D015773:Enalaprilat; D003545:Cysteine