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 studied under conditions suitable for establishing their antioxidant potencies. These phenolic compounds react differently with diphenylpicrylhydrazyl (DPPH) and protect differently sarcoplasmic reticulum membranes against lipid peroxidation induced by Fe2+/ascorbate, as evaluated by the 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 activity and was found to be the most active in inhibiting Fe2+/ascorbate-induced lipid peroxidation. These compounds also exhibit peroxyl radical scavenging activity generated by the water-soluble 2,2'-azobis-(2-amidinopropane hydrochloride) azoinitiator of peroxyl radicals, as evidenced by the inhibition of cis-parinaric acid fluorescence decay or oxygen consumption. 5-ASA rapidly scavenges peroxyl radicals in the aqueous phase, producing a concentration-dependent inhibition period similar to Trolox or cysteine, suggesting an antioxidant activity of chain-breaking type. By comparison, the reactivities of acetaminophen and salicylate are significantly weaker, acting essentially as oxidation retardants. Although closely related in structure, the antioxidant efficiencies 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 stability of the phenoxyl radical. Such a stabilization is not possible with salicylate and is decreased in acetaminophen by an electron withdrawing effect of the p-acetyl.
Dinis
T C
TC
Laboratório de Bioquímica, Faculdade de Farmácia, Universidade de Coimbra, Portugal.
Maderia
V M
VM
Almeida
L M
LM
D000082:Acetaminophen / Q000494:pharmacology*; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D015764:Bepridil / Q000031:analogs & derivatives / Q000378:metabolism; D001713:Biphenyl Compounds; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005297:Ferrozine / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D019804:Mesalamine; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010545:Peroxides; D010851:Picrates; D011817:Rabbits; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000636:Aminosalicylic Acids; D001713:Biphenyl Compounds; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D016166:Free Radical Scavengers; D005609:Free Radicals; D010545:Peroxides; D010851:Picrates; D012459:Salicylates; D017392:Thiobarbituric Acid Reactive Substances; D005297:Ferrozine; C049375:perhydroxyl radical; D000082:Acetaminophen; D019804:Mesalamine; D015764:Bepridil; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; D020156:Salicylic Acid; C013641:parinaric acid