Hepatic reduction of carbamoyl-PROXYL in ferric nitrilotriacetate induced iron overloaded mice: an in vivo ESR study.
Reduction 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.
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400,Thailand. noppawan.phu@mahidol.ac.th
Noppawan Phumala
NP
Morales
Yumiko
Y
Yamaguchi
Kimiyo
K
Murakami
Nuttavut
N
Kosem
Hideo
H
Utsumi
D000818:Animals; D002273:Carcinogens; D003497:Cyclic N-Oxides / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
D002273:Carcinogens; D003497:Cyclic N-Oxides; D005290:Ferric Compounds; D011759:Pyrrolidines; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl; D007501:Iron; D005978:Glutathione; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate