67] Alloxan and 6-hydroxydopamine: Cellular toxins

Abstract

6-Hydroxydopamine and alloxan are cellular toxins with similar modes of action but different tissue specificity. Alloxan, injected in vivo , destroys the insulin-producing β cells of the pancreas to produce an experimental form of diabetes. 6-Hydroxydopamine, on the other hand, destroys catecholamine nerve terminals and cell bodies. The polyphenolic (reduced) forms of both agents react rapidly with molecular oxygen to yield quinoidal products and several forms of reduced oxygen––namely, superoxide and hydroxyl free radicals and hydrogen peroxide. Although the quinones and oxygen metabolites can all contribute to tissue damage, current evidence indicates that it is the reduced forms of oxygen that predominate in the destruction of target tissues. Intermediate semiquinone radicals have not been evaluated for their toxic actions. The toxins destroy those cells in which they accumulate. Tissue reducing agents, such as ascorbate, amplify the cellular toxicity by reducing the quinoidal forms of the cellular toxins. The reduced forms then recycle through oxidative reactions with molecular oxygen to increase a flux of evanescent and destructive free-radical intermediates. Thus, an apparently paradoxical situation arises in which reducing agents amplify oxidative damage.