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.
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 O2- in the systems composed of luteoskyrin, NAD(P)H, and either rat liver microsomal NADPH-cytochrome P-450 reductases or submitochondrial particles and (3) dicoumarol showed no effect on the O2- 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.
Ueno
I
I
Institute of Physical and Chemical Research, Saitama, Japan.
Sekijima
M
M
Hoshino
M
M
Ohya-Nishiguchi
H
H
Ueno
Y
Y
D000818:Animals; D015197:Carcinogenicity Tests; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology; D009183:Mycotoxins / Q000633:toxicity*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009285:Naphthoquinones / Q000633:toxicity*; D010084:Oxidation-Reduction; D010407:Penicillium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D009183:Mycotoxins; D009285:Naphthoquinones; D013481:Superoxides; C100224:luteoskyrin; D009247:NADH, NADPH Oxidoreductases