Contribution of Nitric Oxide to Potassium Bromate-Induced Elevation of Methaemoglobin Concentration in Mouse Blood.

• Watanabe Satoshi

  Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University

• Togashi Shin-ichi

  Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University

• Fukui Tetsuya

  Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University

抄録

Bromate, an inorganic oxyhalide disinfection by-product, is known to cause kidney damage, haemolysis and methaemoglobinemia. In potassium bromate (KBrO₃)-treated mice (1.2 mmol/kg), elevation of methaemoglobin (MetHb) concentration in blood was observed simultaneously with an elevation of the NO concentration and attenuation of glutathione peroxidase (GPx) activity. Renal oxidative stress and kidney damage were also confirmed in the KBrO₃-treated mice. A pre-administered GPx-mimic ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) dose-dependently diminished the KBrO₃-induced changes in MetHb concentration and GPx activity. Renal oxidative stress and kidney damage caused by the KBrO₃ administration were also dose-dependently suppressed by ebselen. On the other hand, ebselen did not suppress the KBrO₃-induced elevation of the NO concentration. KBrO₃-induced methaemoglobinemia, renal oxidative stress and kidney damage, consequently, seemed to result from the attenuation of GPx activity. Besides, the enhancement of NO production was not likely to be a result but a cause for the KBrO₃-induced attenuation of GPx activity. In in vitro experiments, oxidation of human oxy-haemoglobin (HbO₂) to MetHb was observed in a reaction mixture containing HbO₂ and an NO donor, NOC-7 (1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene) or SIN-1 (3-(4-morpholinyl)sydnonimine), and this oxidation was inhibited by the NO scavenger carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide). However, no MetHb formation was observed in a reaction mixture containing HbO₂ and KBrO₃. These results suggest that KBrO₃-induced methaemoglobinemia results from the reduction of GPx activity in blood by the KBrO₃-induced increases in superoxide, NO and ONOO⁻.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 25 (10), 1315-1319, 2002

  公益社団法人 日本薬学会

キーワード

• potassium bromate
• methaemoglobin
• ebselen
• nitric oxide
• glutathione peroxidase

詳細情報

• CRID: 1390282679602742400
• NII論文ID: 110003638902
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.25.1315
• COI: 1:CAS:528:DC%2BD38XosFymsLo%3D
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 6312839
• PubMed: 12392086
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6312839
• Web Site: http://www.jstage.jst.go.jp/article/bpb/25/10/25_10_1315/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2003115349
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
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