Noppawan Phumala MoralesYumiko YamaguchiKimiyo MurakamiNuttavut KosemHideo UtsumiMahidol UniversityKyushu University2018-06-112018-06-112012-07-01Biological and Pharmaceutical Bulletin. Vol.35, No.7 (2012), 1035-104013475215091861582-s2.0-84863543125https://repository.li.mahidol.ac.th/handle/20.500.14594/15162Reduction of a nitroxyl radical, carbamoyl-PROXYL in association of free radical production and hepatic glutathione (GSH) was investigated in iron overloaded mice using an in vivo L-band electron spin resonance (ESR) spectrometer. Significant increases in hepatic iron, lipid peroxidation and decrease in hepatic GSH were observed in mice intraperitoneally (i.p.) administrated with ferric nitrilotriacetate (Fe(III)-NTA, a total 45 μmol/mouse over a period of 3 weeks). Free radical production in iron overloaded mice was evidenced by significantly enhanced rate constant of ESR signal decay of carbamoyl-PROXYL, which was slightly reduced by treatment with iron chelator, deferoxamine. Moreover, the rate constant of ESR signal decay was negatively correlated with hepatic GSH level (r--=0.586, p < 0.001). On the other hand, hepatic GSH-depletion ( > 80%) in mice through daily i.p. injection and drinking water supplementation of L-buthionine-[ S,R]-sulfoximine (BSO) significantly retarded ESR signal decay, while there were no changes in serum aspartate aminotransferase and liver thiobarbituric acid-reactive substances levels. In conclusion, GSH plays two distinguish roles on ESR signal decay of carbamoyl-PROXYL, as an antioxidant and as a reducing agent, dependently on its concentration. Therefore, it should be taken into account in the interpretation of free radical production in each specific experimental setting. © 2012 The Pharmaceutical Society of Japan.Mahidol UniversityPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1248/bpb.b110701