Spin-Trapping and Direct Epr Investigations on the Hepatotoxic and Hepatocarcinogenic Actions of Luteoskyrin, An Anthraquinoid Mycotoxin Produced by Penicillium Islandicum Sopp. Generations of Superoxide Anion and Luteoskyrin Semiquinone Radical in the Redox Systems Consisted of Luteoskyrin and Liver Nadph- Or Nadh-Dependent Reductases |
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Authors: | Ikuko Ueno Masaru Sekijima Mikio Hoshino Hiroaki Ohya-Nishiguchi Yoshio Ueno |
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Institution: |
a Institute of Physical and Chemical Research, Wako, Saitama
b Yamagata Technopolis Foundation, Yamagata, Japan
c Department of Toxicology and Microbiological Chemistry, Science University of Tokyo, Shinjuku, Tokyo |
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Abstract: | Luteoskyrin is a hepatotoxic and hepatocarcinogenic bisdihydroanthraquinone produced by Penicillium islandicum Sopp. By observing the EPR spectra of DMPO-spin adducts and luteoskyrin semiquinone radical, we investigated in vitro whether luteoskyrin is reduced to its semiquinone radical leading to the generation of active oxygen species in redox systems catalyzed by NADPH-dependent cytochrome reductases of the liver. We found (1) the formation of luteoskyrin semiquinone radical in the NADPH-cytochrome P-450 reductase system under anaerobic conditions, (2) the generation of O- in the systems composed of luteoskyrin, NAD(P)H, and either rat liver microsomal NADPH-cytochrome P-450 reductase or submitochondrial particles and (3) dicoumarol showed no effect on the O- generation in the case of submitochondrial particles. From these results we proposed that luteoskyrin liver injuries are induced by the active oxygen species generated in the process of autoxidation of luteoskyrin semiquinone radical which is produced in the one-electron redox systems catalyzed by the liver NAD(P)H-dependent cytochrome reductases. |
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Keywords: | Luteoskyrin semiquinone radical NADPH-cytochrome P-450 reductase NAD(P)H-cytochrome c reductase superoxide EPR hepatocarcinogen mycotoxin Ikuko Ueno |
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