New antioxidants and their metabolites

Project leader: Ao.Univ. Prof. Dr. Lars Gille, University of Veterinary Medicine, Vienna BOKU partner: Ao.Univ. Prof. Dr. Thomas Rosenau; Dept. of Chemistry Oxygen radicals are involved in the pathogenesis of numerous diseases. However, intervention trials involving supplementation of antioxidants to healthy man and animals were only partially successful so far. This might be due to physiological activities of their respective antioxidant metabolites, which may counteract the beneficial effects of antioxidants. The major metabolite of the antioxidant vitamin E is tocopheryl quinone (TQ). It is well known, that quinoid compounds in contact with redox-enzymes can exert prooxidative activity, e.g. by stimulating oxygen radical formation, as well as antioxidant activity in its reduced form. Due to the high redox activity and appropriate binding sites for quinones in mitochondria the interference of TQ with the mitochondrial electron transfer system, and oxygen radical formation can be expected. We hypothesize that the efficiency of vitamin E-type antioxidants can be increased by avoiding the formation of quinoid metabolites from chromanoxyl radical intermediates. This could be achieved by employing novel vitamin E derivatives, which form more stable chromanoxyl radicals. In contrast, the metabolic conversion of the vitamin E-type antioxidant ubichromenol to ubiquinone could be employed to deliver ubiquinone to mitochondria, which is known to improve the mitochondrial energy conservation. These approaches will point out new ways to increase the benefits of antioxidant supplementation, and will improve the understanding of its effects and influencing factors.