The redox reaction and biotransformation of rubroskyrin, a modified bis-anthraquione from Penicillium islandicum Sopp.

Abstract

Rubroskyrin, a modified bis-anthraquinone pigment from Penicillium islandicum Sopp, was studied on the redox interaction with NADH-linked redox system of rat liver microsomes, comparing with luteoskyrin and rugulosin. It was found that rubroskyrin was enzymatically reduced by NADH/microsomes and was immediately autoxidized by dissolved oxygen, producing hydrogen peroxide (H2O2). Luteoskyrin and rugulosin did not exhibit such a redox reaction, consuming dissolved oxygen and producing H2O2. The H2O2 production was significantly accelerated by superoxide dismutase (SOD), suggesting the production of superoxide anion during the reduction-autoxidation cycles of rubroskyrin. The thin layer chromatographic (TLC) and spectrophotometric analyses revealed that rubroskyrin was biotransformed by the NADH/microsomes system to stable product(s) which was no longer enzymatically reduced by the NADH/microsome system. From these results it was speculated that the mutagenicity of rubroskyrin might result from the generation of active oxygen by the NADH/microsome-catalyzed redox reaction, and that the redox reaction-linked biotransformation might lead to the elimination of cytotoxicity of rubroskyrin, showing significantly less toxicity than those of luteoskyrin and rugulosin in vivo.