Document Detail

Contribution of nitric oxide to potassium bromate-induced elevation of methaemoglobin concentration in mouse blood.
MedLine Citation:
PMID:  12392086     Owner:  NLM     Status:  MEDLINE    
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 oxyhaemoglobin (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-.
Satoshi Watanabe; Shin-ichi Togashi; Tetsuya Fukui
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  25     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-23     Completed Date:  2003-04-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1315-9     Citation Subset:  IM    
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
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MeSH Terms
Bromates / pharmacology*
Methemoglobin / biosynthesis,  metabolism*
Nitric Oxide / biosynthesis*
Reg. No./Substance:
0/Bromates; 10102-43-9/Nitric Oxide; 7758-01-2/potassium bromate; 9008-37-1/Methemoglobin

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