ROLE OF HYDROXYL RADICAL IN SUPEROXIDE INDUCED MICROSOMAL LIPID-PEROXIDATION - PROTECTIVE EFFECT OF ANION CHANNEL BLOCKER

Treatment of bovine pulmonary artery smooth muscle microsomes with the superoxide radical generating system hypoxanthine plus xanthine oxida se stimulated iron release, hydroxyl radical production and lipid pero xidation. Pretreatment of the microsomes with deferoxamine or dimethyl thiourea markedly inhibited lipid peroxidation, and prevented hydroxyl radical production without appreciably altering iron release. The sup eroxide radical generating system did not alter the ambient superoxide dismutase activity. However, addition of exogenous superoxide dismuta se prevented superoxide radical induced iron release, hydroxyl radical production and lipid peroxidation Simultaneous treatment of the micro somes with deferoxamine, dimethylthiourea or superoxide dismutase prev ented hydroxyl radical production and liqid peroxidation. While defero xamine or dimethylthiourea did not appreciably alter iron release, sup eroxide dismutase prevented iron release. However, addition of deferox amine, dimethylthiourea or superoxide dismutase even 2 min after treat ment did not significantly inhibit lipid peroxidation, hydroxyl radica l production and iron release. Pretreatment of microsomes with the ani on channel blocker 4,4'-dithiocyano 2,2'-disulphonic acid stilbine did not cause any discernible change In chemiluminiscence induced by the superoxide radical generating system but markedly inhibited lipid pero xidation without appreciably altering iron release and hydroxial radic al production.