Heparin: does it act as an antioxidant in vivo?

Previous studies have shown that heparin antagonizes oxygen radical-mediated injury to endothelial cells, suggesting an antioxidant role of the drug. In the present investigation, the hypothesis that heparin exerts direct antioxidant effects was tested in several experimental models. We have found that 1, 3, 5, 10, 20, 40 and 80 U/mL of heparin do not scavenge superoxide anion, hydrogen peroxide, hydroxyl radical or the stable free radical 1,1-diphenyl-2-pycrylhydrazyl. Moreover, the drug is ineffective towards iron-driven linolenic acid peroxidation, autooxidation of brain homogenate and linolenic acid peroxidation mediated by human internal mammary artery homogenate. Specific studies on the potential iron-binding-inactivating capacity of heparin prove the drug to be totally ineffective. Finally, the loss of protein sulphydryls from human plasma induced by hypoxanthine-xanthine oxidase-generated oxygen radicals is not prevented by heparin. In conclusion, heparin, even at concentrations far higher than those usually used therapeutically, has no direct antioxidant properties. Thus, other mechanisms not strictly antioxidant-type must be involved in heparin-mediated cell protection against toxic oxygen metabolites.