ACTION OF PHENOLIC DERIVATIVES (ACETAMINOPHEN, SALICYLATE, AND 5-AMINOSALICYLATE) AS INHIBITORS OF MEMBRANE LIPID-PEROXIDATION AND AS PEROXYL RADICAL SCAVENGERS

The action of the phenolic compounds acetaminophen, salicylate, and 5- aminosalicylate (5-ASA) as inhibitors of lipid peroxidation was studie d under conditions suitable for establishing their antioxidant potenci es. These phenolic compounds react differently with diphenylpicrylhydr azyl (DPPH) and protect differently sarcoplasmic reticulum membranes a gainst lipid peroxidation induced by Fe2+/ascorbate, as evaluated by t he formation of thiobarbituric acid-reactive substances (TBARS) and by the loss of the polyunsaturated fatty acyl chains. 5-Aminosalicylate reacts promptly with DPPH, suggesting a potent radical scavenger activ ity and was found to be the most active in inhibiting Fe2+/ascorbate-i nduced lipid peroxidation. These compounds also exhibit peroxyl radica l scavenging activity generated by the water-soluble 2,2'-azobis-(2-am idinopropane hydrochloride) azoinitiator of peroxyl radicals, as evide nced by the inhibition of cis-parinaric acid fluorescence decay or oxy gen consumption. 5-ASA rapidly scavenges peroxyl radicals in the aqueo us phase, producing a concentration-dependent inhibition period simila r to Trolox or cysteine, suggesting an antioxidant activity of chain-b reaking type. By comparison, the reactivities of acetaminophen and sal icylate are significantly weaker, acting essentially as oxidation reta rdants. Although closely related in structure, the antioxidant efficie ncies of the three phenolic compounds are significantly different. The higher antioxidant activity of 5-ASA is putatively related with the p -amine relative to the hydroxyl group, potentially increasing the stab ility of the phenoxyl radical. Such a stabilization is not possible wi th salicylate and is decreased in acetaminophen by an electron withdra wing effect of the p-acetyl. (C) 1994 Academic Press, Inc.