H-2-RECEPTOR ANTAGONISTS ARE SCAVENGERS OF OXYGEN RADICALS

Potential oxygen radical scavenging properties of the Hz-receptor antagonists cimetidine, ranitidine and famotidine were investigated. These drugs, although ineffective against superoxide anion and hydrogen peroxide, can scavenge hydroxyl radical (OH.) with a very high rate constant, which is about tenfold higher than that of the specific scavenger mannitol for famotidine (1.7 x 10(10) mol(-1) s(-1)) and cimetidine (l.6 x 10(10) mol(-1) s(-1)), ranitidine displaying a rate constant of 7.5 x 10(9) mol(-1) s(-1). These OH. scavenging effects are significant beginning from 10, 28 and 100 mu mol l(-1) concentration for famotidine, cimetidine and ranitidine, respectively, thus suggesting that the drugs may effectively act as OH scavengers in vivo especially in the gastric lumen. Only cimetidine can apparently bind and inactivate iron, which further emphasizes its antioxidant capacity. Moreover, all drugs, even at 10 mu mol l(-1) concentration, show powerful scavenging effects on hypochlorous acid and monochloramine, which are cytotoxic oxidants arising from inflammatory cells, such as neutrophils. These data suggest that some therapeutical effects of H-2-receptor antagonists in peptic ulcer may also be related to their antiradical-antioxidant capacity, and that these drugs could potentially be used in other disease entities characterized by free radical-mediated oxidative stress in vivo.