Inhibition by heparin of Fe(II)-catalysed free-radical peroxidation of linolenic acid

Abstract

Heparin, in a concentration-dependent manner, inhibited the generation of conjugated dienes and thiobarbituric acid-positive substances when incubated with Fe2+ and gamma-linolenic acid. In the conjugated diene assay, other glycosaminoglycans, on a molar basis calculated with respect to their respective hydrated disaccharide repeat units, were less effective than heparin. Heparin which had been re-N-sulphonated after removal of both N-sulphonates and O-sulphates, and heparin in which iduronate residues had been reduced to idose residues, were largely unaffected in their activity. Removal of both N-sulphonates and O-sulphates greatly reduced the effectiveness of the heparin. Analysis of the effects of heparin fragments generated by heparinase I treatment of heparin showed that depolymerization decreased the effectiveness of the heparin. It is possible that heparins and related strongly acidic polysaccharides may function as endogenous antioxidants, and that sequestration by them, or harmless oxidation by them, of ions such as Fe2+, contributes to their effectiveness.

The effect of heparin on Cu2+‐mediated oxidation of human low‐density lipoproteins

“…This phenomenon could be explained on the basis of two different mechanisms: (1) a partial sequestration of Cu 2÷ by the polyanion chain of HE; (2) the possible change in the ability of LDL to bind Cu 2+, due to the structural modification of the particle following the interaction with HE. HE was shown to inhibit Fe2+-catalyzed peroxidation of 7/-linolenic acid [7]. Our study emphasizes that the antioxidant effect of HE protects not only a free fatty acid, but also a biological structure, such as human LDL against Cu2+-induced oxidation.…”

Heparin protection against Fe2+‐and Cu2+‐mediated oxidation of liposomes

“…Recent findings suggest that HE may als,) play a protective role in oxidative stress. In fact, HE was found to inhibit the generation of conjugated dienes and thiobarbituric acid reactive substances (TBARS) when incubated wi~h Fe 2-and 7-1inolenic acid [4]. Moreover, an antioxidant efft:ct of HE was shown on Cu2+-mediated oxidation of human LDL [5].…”

Is Encephalopathy a Mechanism to Renew Sulfate in Autism?

“…A plausible basis for a rate-enhancing effect of HS desulfation on bacterial glycolipid breakdown may be inferred from a report of a protective effect of a highly sulfated polysaccharide, heparin, against Fe 2+ -catalyzed lipid peroxidation in vitro [62]. In this study, fully-sulfated heparin exhibited much greater antioxidant activity than modified heparin from which the N-and O-sulfate groups had been removed.…”