Roles of in vivo REDOX systems by using in vivo ESR and transgenic mice

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Reactive oxygen species and free radicals have important roles in physiological phenomena and diseases. There are discrepancy in the roles of antioxidative enzymes or antioxidants between in vitro and in vivo experiments. It is, therefore, important to investigate in vivo free radical reactions, to clarify roles of in vivo redox enzymes.In this study, role of Cu/Zn SOD was investigated under several kinds of oxidative stress using electron spin resonance (ESR) technique and Cu/Zn-SOD transgenic mice. In vivo ESR technique is the unique detection method to measure in vivo free radical reactions non-invasively.In physiological condition, it was indicated using newly synthesized redox probe that redox balances in SOD-Transgenics was changed. Overexpression of Cu/Zn-SOD on free radical reactions caused by 2,4,6-trichlorophenol (TCP) was also investigated using Cu/Zn-SOD transgenic mice and in vivo ESR spectroscopy. TCP enhanced free radical reactions in upper abdomen and increased serum GOT in a dose dependent manner. These enhancements were suppressed both by antioxidant and by overexpression of Cu/Zn-SOD,suggesting the relation of free radicals with liver injury caused by TCP and the suppression effect of endogenous Cu/Zn-SOD.Results of this study indicates that combination of transgenic animals and in vivo ESR technique will be useful to clarify the role of redox enzymes in diseases.