Novel antioxidant effects of deuterated polyunsaturated fatty acids against lipid peroxidation in cell membranes: Hypothesis paper

Lipid peroxidation (LPO) has long been implicated in the pathogenesis of various diseases and the role of antioxidants against LPO has been studied extensively. Recently, novel antioxidant functions of deuterated polyunsaturated fatty acids (D-PUFAs) in preventing LPO in the membranes and in humans have been reported by many research groups. The preventive and therapeutic potential of D-PUFAs against LPO and related diseases has received considerable attention, but the underlying molecular mechanisms and dynamics remain elusive. This hypothesis article summarizes state of the art preventive effects of D-PUFAs against LPO and cell damage reported in the literature and discusses the plausible mechanisms of action with an emphasis on the effects of membrane properties. Interestingly, it was found that cholesterol and oleic acid as well as D-PUFAs did not inhibit LPO in homogeneous solution, but they all suppressed LPO in the liposomal membranes, cell membranes, and partially in vivo. It is speculated that D-PUFAs suppress LPO in the membranes, at least in part, by physically obstructing the reaction between lipid peroxyl radicals and phospholipid substrates as well as by chemical and biochemical mechanisms. However, the proposed mechanism remains a hypothesis which should be validated directly in future experimental studies.