Double lipoxygenation of polyunsaturated fatty acids of nutritional interest

•PUFA with at least three methylene-interrupted double bonds may undergo a double lipoxygenation, leading to trans,cis,trans/E,Z,E conjugated trienes.•The reduced products are di-OH-E,Z,E which inhibit platelet cyclooxygenase (COX) activity and the aggregating effect of the PGH2/TxA2 COX products.•In addition to these platelet effects, the 10,17-di-OH-E,Z,E product from docosahexaenoic acid, called protectin DX, has been described active against diverse pathophysiological situations, such as influenza virus proliferation, insulin and glucose related metabolic diseases, and white cells involved in vascular disorders. Double lipoxygenation of polyunsaturated fatty acids having at least three methylene-interrupted double bonds can be made by two lipoxygenases, e.g. 5- and 12-LOX, or 15-LOX only, followed by reduction of the hydroperoxide products through the glutathione peroxidase action. Several biological activities have been reported for such a double 15-LOX product of docosahexaenoic acid, called protectin DX to differentiate it from protectin D1, a stereo and geometric isomer described for its potent anti-inflammatory potential. The geometric characteristic of the double lipoxygenase products is the conjugated triene E,Z,E (trans,cis,trans), which appears crucial in their biological activities. A focus is also done on single lipoxygenation of mono-hydroxylated products first made by aspirin-treated cyclooxygenase-2. The resulting (R,S)-diOH, E,Z,E conjugated trienes, instead of the (S,S)-diOH isomer in case of double lipoxygenation, seem to be even more active for some biological effects, making biologically relevant the single lipoxygenation in aspirin-treated situations.