Protective effects of carnosine and homocarnosine on ferritin and hydrogen peroxide-mediated DNA damage

Previous studies have shown that one of the primary causes of increased iron content in the brain may be the release of excess iron from intracellular iron storage molecules such as ferritin. Free iron generates ROS that cause oxidative cell damage. Carnosine and related compounds such as endogenous histidine dipetides have antioxidant activities. We have investigated the protective effects of carnosine and homocarnosine against oxidative damage of DNA induced by reaction of ferritin with H(2)O(2). The results show that carnosine and homocarnosine prevented ferritin/H(2)O(2)-mediated DNA strand breakage. These compounds effectively inhibited ferritin/H(2)O(2)-mediated hydroxyl radical generation and decreased the mutagenicity of DNA induced by the ferritin÷H(2)O(2) reaction. Our results suggest that carnosine and related compounds might have antioxidant effects on DNA under pathophysiological conditions leading to degenerative damage such as neurodegenerative disorders.