Influence of chondroitin sulfate charge density, sulfate group position, and molecular mass on Cu2+-mediated oxidation of human low-density lipoproteins: effect of normal human plasma-derived chondroitin sulfate.

The effects of chondroitin sulfate samples with decreasing charge densities, different 4-sulfate/6-sulfate ratios, and various molecular masses on Cu2+-induced oxidation of human low-density lipoprotein (LDL) were evaluated by monitoring conjugated diene formation and the tryptophan fluorescence kinetics. Low-sulfated chondroitin sulfate (CS) from beef trachea had a very strong protective antioxidant effect. Quite similar behavior was observed for CS from pig trachea, and a fructose-containing polysaccharide with a chondroitin backbone from Escherichia coli was also strongly protective as to LDL oxidation. CS samples with decreasing charge densities proved effective in inhibiting LDL oxidation. A totally desulfated sample still exhibited a great capacity to protect LDL against oxidation. CS-4-sulfate samples (sulfate to carboxyl ratio of 0.62, about 65% 4-sulfate groups and 5% 6-sulfate groups) retained great ability to inhibit the Cu2+-mediated human LDL oxidation. CS fractions with different molecular masses were examined as possible inhibitors of LDL oxidation. Samples with molecular masses lower than about 8,570 (13-15 disaccharide units) were unable to protect human LDL from Cu2+-induced oxidation. Similar results were obtained on studying the degradation of tryptophan residues of the LDL protein moiety resulting from Cu2+ complexation through amino acid residues. A low-sulfated CS (sulfate to carboxyl ratio of 0.41, a molecular mass of about 15,600) having effective anti-oxidant properties as to metal-induced LDL oxidation was isolated from normal human plasma. The protective capacity as to Cu2+-mediated LDL oxidation of CS is discussed in relation to its structure, also considering the physiological role of plasma CS in relation to factors that can alter its properties.