Inhibition of lipid peroxidation by pindolol.

Abstract

Among beta-blockers, including atenolol, metaproterenol, pindolol and propranolol, only pindolol strongly inhibited lipid peroxidation induced by xanthine oxidase-hypoxanthine in the presence of adenosine-5'-phosphate-Fe3+. In the reaction system, superoxide predominantly reduced iron because superoxide dismutase strongly prevented the iron reduction. However, pindolol had no effect on the superoxide-dependent iron reduction. Adding superoxide dismutase immediately stopped the lipid peroxidation, indicating that superoxide is closely connected with forming the initiator of xanthine oxidase-hypoxanthine-induced lipid peroxidation. On the other hand, pindolol also inhibited lipid peroxidation, whereas it did not react with superoxide, indicating that it inhibited xanthine oxidase-hypoxanthine-induced lipid peroxidation by an independent mechanism of superoxide. Pindolol sharply scavenged 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) radical cations, but the ability of pindolol to scavenge peroxyl radicals of 2,2'-azobis(2-amidinopropane)-dihydrochloride and 2,2'-diphenyl-p-picrylhydrazyl radicals was low. In addition, pindolol did not scavenge hydroxyl radicals at physiologically significant concentrations. These results suggest that the ability of pindolol to inhibit lipid peroxidation was due to scavenging carbon-centered radicals rather than peroxyl radicals.