Hematological Effects of Chlorine Dioxide on In Vitro Exposure in Mouse, Rat and Human Blood and on Subchronic Exposure in Mice
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概要
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Hematological effects of chlorine dioxide (ClO_2) and its metabolites were investigated. In vitro exposure of mouse, rat and human blood cells to ClO_2 and the reduction by-product, chlorite (ClO_2^-) resulted in the formation of methemoglobin, a decrease in the activities of glucose-6-phosphate dehydrogenase (G-6-PD) and glutathione peroxidase (GPX) and in the content of reduced glutathione (GSH), and an increase in hydrogen peroxide (H_2O_2) formation and hemolysis. The H_2O_2 formation and hemolysis induced by ClO_2 and ClO_2 ^- in mouse blood cells were the highest among cells tested, and human blood cells were more resistant to the oxidative stress than rat and mouse blood cells. Both compounds also showed more toxic responses to E. coli mutants lacking production of catalase DSH19 (katEG), superoxide dismutase DSH56 (sodAB) and both of them DSH67 (katEG sodAB) than the wild strain DSH7 by Kat-sod assay, as a biological detection method for reactive oxygen species, suggesting the production of H_2O_2 and superioxide anion. For subchronic study of ClO_2,mice received drinking water containing 100,1000,1500 or 2000mg/l ClO_2 in the presence of the stabilizer, 1200mg/l of sodium bicarbonate ad libitum for 30,60 or 90days. Statistically significant hematological changes were observed in animals exposed to more than 1000mg/l ClO_2,which showed augmented G-6-PD activity in erythrocytes and increased resistance to hemolysis in hypotonic solution. The results of this study therefore indicate that ClO_2 acutely causes hematotoxicity toward mice by producing reactive oxygen species and by weakening the protection systems to oxidative stress in erythrocytes, although the latter may be induced by long term exposure, while humans appear to be more resistant to this hematotoxicity.
- 公益社団法人日本薬学会の論文
- 2000-04-01
著者
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Ueno Hitoshi
Dep. Of Public Health & Preventive Pharmacology Fac. Of Pharmaceutical Sciences Setsunan Univ.
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Ueno Hitoshi
Department Of Public Health & Preventive Pharmacology Faculty Of Pharmaceutical Sciences Setsuna
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Ueno Hitoshi
Faculty of Pharmaceutical Sciences, Setsunan University
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Sayato Yasuyoshi
Faculty of Pharmaceutical Sciences, Setsunan University
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Nakamuro Katsuhiko
Faculty of Pharmaceutical Sciences, Setsunan University
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Nakamuro K
Department Of Public Health & Preventive Pharmacology Faculty Of Pharmaceutical Sciences Setsuna
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Nakamuro Katsuhiko
Faculty Of Pharmaceutical Sciences Setsunan University
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Sayato Yasuyoshi
Faculty Of Pharmaceutical Sciences Setsunan University
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