Direct and respiratory chain-mediated redox cycling of adrenochrome

Adrenochrome is reduced by ascorbate in a reaction accompanied by a large and rapid oxygen uptake. The rates of adrenochrome reduction and the concomitant oxygen uptake are decreased in the presence of superoxide dismutase or catalase. The species formed on the one-electron reduction of adrenochrome (i.e., the semiquinone) was shown by pulse radiolysis to rapidly react with oxygen (9.10(8) M-1.s-1), indicating the occurrence of a redox cycling in a system formed by adrenochrome, a reducing agent, and oxygen. Adrenochrome is also reduced to the corresponding semiquinone by complex I of beef heart submitochondrial particles supplemented with NADH, while succinate is unable to support this reduction. The o-semiquinone is the intermediate species in the superoxide-generating cycle resulting from both non-enzymatic and enzymatic reduction. The toxic effects of adrenochrome and its pathophysiological role can be explained, at least in part, on the basis of the demonstrated cycle.