The redox reaction and biotransformation of rubroskyrin, a modified bis-anthraquione from Penicillium islandicum Sopp.
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.
Mori
S
S
Department of Biochemistry, Gifu University School of Medicine, Japan.
Kawai
K
K
Nozawa
Y
Y
Ogihara
Y
Y
D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D003579:Cytochrome Reductases / Q000378:metabolism*; D042966:Cytochrome-B(5) Reductase; D008862:Microsomes, Liver / Q000378:metabolism*; D009183:Mycotoxins / Q000737:chemistry / Q000493:pharmacokinetics*; D009285:Naphthoquinones / Q000494:pharmacology; D010084:Oxidation-Reduction; D010407:Penicillium / Q000737:chemistry*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D000880:Anthraquinones; D009183:Mycotoxins; D009285:Naphthoquinones; C100224:luteoskyrin; C029548:rugulosin; D013482:Superoxide Dismutase; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; C009274:skyrin