Diphenylamine: an unusual antioxidant.
Diphenylamine (DPA) has been utilized as an antioxidant in studies of lipid peroxidation. Using peroxidizing red blood cell (RBC) membranes, we find that DPA actually promotes lipid hydroperoxide (LOOH) formation and oxygen consumption while markedly inhibiting generation of thiobarbituric acid reactive substances (TBARS). As a consequence, DPA increases the prelytic RBC K leak that results from peroxidative stress and potentiates a known nonprelytic but LOOH-dependent K leak pathway in RBC. In contrast, DPA abolishes formation of cyclooxygenase-dependent conversion products of arachidonate. DPA is almost as efficient as BHT in inhibiting peroxyl radical mediated destruction of phycoerythrin fluorescence. Study of DPA analogues shows that the antioxidant effect of DPA lies in its secondary amine function. Presumably, this results in intermediate formation of a nitrogen-based radical so that redox cycling of this aromatic amine stimulates further peroxidation. This dramatically illustrates the hazard of relying solely on TBARS measurements for assessment of peroxidation.
Sugihara
T
T
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Rao
G
G
Hebbel
R P
RP
D000975:Antioxidants / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004159:Diphenylamine / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D005609:Free Radicals; D010545:Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D002084:Butylated Hydroxytoluene; D020122:tert-Butylhydroperoxide; D004159:Diphenylamine