RETINOIC ACID-DEPENDENT STIMULATION OF 2,2'-AZOBIS(2-AMIDINOPROPANE)-INITIATED AUTOXIDATION OF LINOLEIC-ACID IN SODIUM DODECYL-SULFATE MICELLES - A NOVEL PROOXIDANT EFFECT OF RETINOIC ACID

(E)-Retinoic acid (RA) was shown to stimulate the rate of 2,2'-azobis( 2-amidinopropane) (AAPH)-initiated autoxidation of linoleic acid (18:2 ) in sodium dodecyl sulfate (SDS) micelles. RA-dependent stimulation o f 18:2 autoxidation was characterized by enhanced rates of dioxygen up take which were linear with retinoid concentration. In contrast, 5,6-e poxy-RA, a major oxidation product of RA, failed to affect the rate of dioxygen consumption at all concentrations tested. RA was also shown to stimulate peroxyl radical-dependent oxidation of styrene to the cor responding oxirane when styrene was included in the micellar system as a molecular probe. Furthermore, unequivocal evidence of RA-dependent stimulation of 18:2 autoxidation was obtained by relative quantitation of 13-hydroxy-(9Z,11E)-octadecadienoic acid (13-HODE) plus 9-hydroxy- (10E,12Z)-octadecadienoic acid (9-HODE) production. In addition, enhan ced carbon-centered radical formation was demonstrated in the presence of RA by EPR spectroscopy using alpha-(4-pyridyl 1-oxide)-N-tert-buty lnitrone (4-POBN) as a spin trap. Analysis and quantitation of RA oxid ation products indicated that RA was oxidized to one primary product, 5,6-epoxy-RA, which was identified on the basis of cochromatography wi th synthetic standard (in a reverse-phase HPLC system), electronic abs orption spectroscopy, and positive chemical ionization mass spectromet ry of the corresponding methyl ester. Other minor oxidation products w ere also detected but not characterized. In contrast, reaction mixture s devoid of 18:2 failed to demonstrate significant retinoid oxidation. Mechanisms are proposed to account for the prooxidant effects of RA i n this system.