Vanadyl as a catalyst of human lipoprotein oxidation

Lipoprotein oxidation, which is relevant to atherogenesis, can be induced by redox-active transition metals, such as copper. Vanadium is a metal usually used as vanadyl to improve metabolic control in diabetic patients; given its redox-active properties, we have investigated possible oxidative effects of the metal on lipoproteins from healthy and diabetic subjects. Beginning from 10 microM, vanadyl, but not vanadate, induced oxidation of the non-HDL fraction, which was inhibited by EDTA, butylated hydroxytoluene and Vitamins E and C, but not by mannitol, SOD and catalase. Differently from copper, vanadyl could oxidize directly lipoprotein lipids, although it showed a lower oxidant activity against critical tryptophan residues of the lipoprotein protein moiety. Moreover, the non-HDL fraction of diabetic patients was more susceptible to vanadyl-dependent oxidation than that of controls. Thus, vanadium, in its reduced form which may be used in humans, can oxidize the non-HDL fraction through oxidative effects exerted especially on lipoprotein lipids; the specific pro-oxidant activity of vanadyl is more evident with lipoproteins of diabetic patients. Given also the tissue accumulating capacity of vanadium conceivably in a reduced form, its prolonged administration to humans, especially to diabetic patients without adequate antioxidant supplementation, needs caution.