Effect of d-alpha-tocopherol analogues on lipoxygenase-dependent peroxidation of phospholipid-bile salt micelles

In order to know whether or not vitamin E acts as an effective antioxidant in lipoxygenase-dependent peroxidation of phospholipids, the effect of vitamin E and vitamin E analogues, 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMC) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox C), was investigated in enzymatic lipid peroxidation of bile salt micelles of pig liver phosphatidylcholine (PC) using soybean lipoxygenase. 15-Hydroperoxy-5,8,11,13-eicosatetraenoic acid was exclusively produced by the reaction with the PC molecular species containing arachidonic acid moiety, indicating that the hydroperoxidation of pig liver PC entirely progresses through the enzymatic reaction. PMC suppressed the accumulation of PC-hydroperoxides (PC-OOH) more efficiently than either d-alpha-tocopherol (alpha-Toc) or Trolox C, and 50% inhibition concentration by PMC was close to that of quercetin, a known lipoxygenase inhibitor from natural origin. The antioxidant activity of PMC was also superior to that of either alpha-Toc or Trolox C in ferrous ion-induced nonenzymatic oxidation of PC micelles in the presence of a trace amount of PC-OOH, although the radical-scavenging activities of these compounds in solution were similar or comparable to one another. In conclusion, PMC is more effective than alpha-Toc as an inhibitor of lipoxygenase reaction with phospholipids and of autoxidation in phospholipids. The phytyl chain of alpha-Toc seems to be unfavorable for exerting an inhibitory effect on lipoxygenase reaction with phospholipid-bile salt micelles.