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-DEPENDENT OR NADH-DEPENDENT REDUCTASES

Luteoskyrin is a hepatotoxic and hepatocarcinogenic bisdihydroanthraqu inone produced by Penicillium islandicum Sopp. By observing the EPR sp ectra of DMPO-spin adducts and luteoskyrin semiquinone radical, we inv estigated in vitro whether luteoskyrin is reduced to its semiquinone r adical leading to the generation of active oxygen species in redox sys tems catalyzed by NADPH-dependent cytochrome reductases of the liver. We found (1) the formation of luteoskyrin semiquinone radical in the N ADPH-cytochrome P-450 reductase system under anaerobic conditions, (2) the generation of O-2(-) 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 t he O-2(-) generation in the case of submitochondrial particles. From t hese results we proposed that luteoskyrin liver injuries are induced b y the active oxygen species generated in the process of autoxidation o f luteoskyrin semiquinone radical which is produced in the one-electro n redox systems catalyzed by the liver NAD(P)H-dependent cytochrome re ductases.