Oxygen radical generation in human platelets: dependence on 12-lipoxygenase activity and on the glutathione cycle

Stimulation of the arachidonic acid metabolism in human platelets also induces chemiluminescence, which indicates the formation of highly reactive oxygen species. To analyze the pathway by which oxygen radicals are generated, we tested the dependence of O2- generation on the eicosanoid metabolism. We found that inhibition of lipoxygenase, but not of cyclooxygenase, prevented the O2- production. Moreover, depletion of cellular glutathione peroxidase resulted in reduced synthesis of the lipoxygenase product 12-hydroxyeicosatetraenoic acid, as well as in reduce O2- thus establishing a link between O2- generation, the lipoxygenase pathway and the glutathione cycle.