Carboxyfullerene prevents iron-induced oxidative stress in rat brain

Carboxyfullerene, a water-soluble carboxylic acid derivative of a fullerene , was investigated as a protective agent against iron-induced oxidative str ess in the nigrostriatal dopaminergic system of anesthetized rats. Intranig ral infusion of exclusive carboxyfullerene did not increase lipid peroxidat ion in substa nigra or deplete dopamine content in striatum. Infusion of fe rrous citrate (iron II) induced degeneration of the nigrostriatal dopaminer gic system, An increase in lipid peroxidation in substantia nigra as well a s decreases in K+-evoked dopamine overflow and dopamine content in striatum were observed 7 days after the infusion. Go-infusion of carboxyfullerene p revented iron-induced oxidative injury. Furthermore, tyrosine hydroxylase-i mmunoreactive staining showed that carboxyfullerene inhibited the iron-indu ced loss of the dopaminergic nerve terminals in striatum. The antioxidative action of carboxyfullerene was verified by in vitro studies. Incubation of brain homogenates increased the formation of the Schiff base fluorescent p roducts of malonaldehyde, an indicator of lipid peroxidation. Both autooxid ation (without exogenous iron) and iron-induced elevation of lipid peroxida tion of brain homogenates were suppressed by carboxyfullerene in a dose-dep endent manner. Our results suggest that intranigral infusion of carboxyfull erene appears to be nontoxic to the nigrostriatal dopaminergic system. Furt hermore, the potent antioxidative action of carboxyfullerene protects the n igrostriatal dopaminergic system from iron-induced oxidative injury.