Captopril--a potential free radical scavenger: inhibition of PMN NADPH oxidase.
We postulated that Captopril may be capable of acting as a scavenger of free radicals, and performed in vitro studies using harvested human neutrophils. We studied the effect of Captopril on the reduction of Fe3+ cytochrome c by stimulated PMN's. Captopril acts as a reducing agent in this system, and is capable of reducing Fe3+ cytochrome c by itself. NADPH oxidase was harvested from PMA-stimulated human PMN's. Captopril inhibited the activity of this enzyme as assessed by the disappearance of NADPH determined spectrophotometrically. Since similar inhibition could be demonstrated with the superoxide scavenger superoxide dismutase, further studies were conducted using a DTNB assay of the terminal sulfhydryl group of Captopril, in the presence of a biochemical generator of superoxide (hypoxanthine/xanthine oxidase). We were unable to demonstrate disappearance of the thiol group in this system, suggesting that reaction of the SH group with 02- is unlikely under our conditions. We conclude that Captopril may interfere with human PMN NADPH oxidase in vitro.
Egan
T M
TM
Department of Surgery, University of Toronto, Ontario.
Minta
J O
JO
Scrimgeour
K G
KG
Cooper
J D
JD
D002216:Captopril / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002712:Chlorides; D003574:Cytochrome c Group / Q000378:metabolism; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000097:blood*; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase; D014970:Xanthines
D002712:Chlorides; D003574:Cytochrome c Group; D005609:Free Radicals; D017895:Manganese Compounds; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D008345:Manganese; D009249:NADP; D004228:Dithionitrobenzoic Acid; D002216:Captopril; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate; C025340:manganese chloride