Contribution of nitric oxide to potassium bromate-induced elevation of methaemoglobin concentration in mouse blood.
(9/58)
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-. (+info)
High accumulation of oxidative DNA damage, 8-hydroxyguanine, in Mmh/Ogg1 deficient mice by chronic oxidative stress.
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8-Hydroxyguanine (8-OH-G) is a major pre-mutagenic lesion generated from reactive oxygen species. The Mmh/Ogg1 gene product plays a major role in maintaining genetic integrity by removing 8-OH-G by way of the base excision repair pathway. To investigate how oxidative stress influences the formation of 8-OH-G in Ogg1 mutant mice, a known oxidative agent, potassium bromate (KBrO(3)), was administered at a dose of 2 g/l in the drinking water to Ogg1(+/+), Ogg1(+/-) and Ogg1(-/-) mice for 12 weeks. Apurinic (AP) site lyase activity, measured by the excision of 8-OH-G from synthetic oligonucleotides, remained unchanged in kidney cell extracts isolated from Ogg1 mutant mice when the mice were pre-treated by KBrO(3). The levels of 8-OH-G in kidney DNA tremendously increased in a time-dependent manner following exposure of Ogg1(-/-) mice to KBrO(3). Of particular note, the amount of 8-OH-G in kidney DNA from Ogg1(-/-) mice treated with KBrO(3) was approximately 70 times that of KBrO(3)-treated Ogg1(+/+) mice. The accumulated 8-OH-G did not decrease 4 weeks after discontinuing treatment with KBrO(3). KBrO(3) treatment for 12 weeks gave rise to increased mutation frequencies at the transgenic gpt gene in Ogg1(+/+) mice kidney. Absence of the Ogg1 gene further enhanced the mutation frequency. Sequence data obtained from gpt mutants showed that the accumulated 8-OH-G caused mainly GC-->TA transversion and deletion. Other mutations including GC-->AT transition also showed a tendency to increase. These results indicate that 8-OH-G, produced by chronic exposure to exogenous oxidative stress agents, is not repaired to any significant extent within the overall genome of Ogg1(-/-) mice kidney. (+info)
Cell proliferation in liver of Mmh/Ogg1-deficient mice enhances mutation frequency because of the presence of 8-hydroxyguanine in DNA.
(11/58)
The Mmh/Ogg1 gene product maintains the integrity of the genome by removing the damaged base 8-hydroxyguanine (8-OH-G), one of the major DNA lesions generated by reactive oxygen species. Using Ogg1-deficient mice, we sought to establish if cells having high amounts of 8-OH-G have the ability to proliferate and whether the mutation frequency increases after proliferation in vivo. When KBrO(3), a known renal carcinogen, at a dose of 2 grams/liter was administered to Ogg1 mutant mice for 12 weeks, the amount of 8-OH-G in liver DNA from treated Ogg1(-/-) mice increased 26.1 times that of treated Ogg1(+/+) mice. The accumulated 8-OH-G did not decrease 4 weeks after cessation of KBrO(3) treatment. Partial hepatectomy was performed on Ogg1(+/-) and Ogg1(-/-) mice after being treated with KBrO(3) for 12 weeks. The remnant liver from Ogg1(-/-) mice treated with KBrO(3) regenerated to the same extent as nontreated Ogg1(+/-) mice. In addition, 8-OH-G was not repaired during cell proliferation by partial hepatectomy, indicating that there is no replication coupled repair of preexisting 8-OH-G. The mutation frequency after the regeneration of liver from treated Ogg1(-/-) mice showed a 3.5-fold increase compared with before regeneration. This represents a mutation frequency 6.2 times that of normal levels. The proliferation of cells having accumulated amounts of 8-OH-G caused mainly GC-->TA transversions. These results showed that inactivation of the Ogg1 gene leads to a higher risk of cancer because cells with accumulated 8-OH-G still retain the ability to proliferate, leading to an increase in the mutation frequency. (+info)
Flow-injection chemiluminescence determination of formaldehyde with a bromate-rhodamine 6G system.
(12/58)
In this paper, a novel flow-injection chemiluminescence (CL) system for the determination of formaldehyde is described. It is based on a strong enhance effect of formaldehyde on the weak CL emission of the reaction between potassium bromate and rhodamine 6G in a sulfuric acid medium. A possible mechanism for this CL reaction is proposed. A CL calibration graph was linear in the range of 0.8 - 200 microg l(-1) and the detection limit was 0.3 microg l(-1) (3sigma). The relative standard deviation was less than 3% for 10 microg l(-1) formaldehyde (n = 11). The method has been applied to determine formaldehyde in the air samples. (+info)
Endogenous formation of novel halogenated 2'-deoxycytidine. Hypohalous acid-mediated DNA modification at the site of inflammation.
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A potential role of DNA damage by leukocyte-derived reactive species in carcinogenesis has been suggested. Leukocyte-derived peroxidases, such as myeloperoxidase and eosinophil peroxidase, use hydrogen peroxide and halides (Cl- and Br-) to generate hypohalous acids (HOCl and HOBr), halogenating intermediates. It has been suggested that these oxidants lead to the formation of halogenated products upon reaction with nucleobases. To verify the consequences of phagocyte-mediated DNA damage at the site of inflammation, we developed a novel monoclonal antibody (mAb2D3) that recognizes the hypohalous acid-modified DNA and found that the antibody most significantly recognized HOCl/HOBr-modified 2'-deoxycytidine residues. The immunoreactivity of HOCl-treated oligonucleotide was attenuated by excess methionine, suggesting that chloramine-like species may be the plausible epitopes of the antibody. On the basis of further characterization combined with mass spectrometric analysis, the epitopes of mAb2D3 were determined to be novel N4,5-dihalogenated 2'-deoxycytidine residues. The formation of the dihalogenated 2'-deoxycytidine in vivo was immunohistochemically demonstrated in the lung and liver nuclei of mice treated with lipopolysaccharides, an experimental inflammatory model. These results strongly suggest that phagocyte-derived oxidants, hypohalous acids, endogenously generate the halogenated DNA bases such as a novel dihalogenated 2'-deoxycytidine in vivo. Halogenation (chlorination and/or bromination) of DNA therefore may constitute one mechanism for oxidative DNA damage at the site of inflammation. (+info)
Cyclodextrin-aided determination of iodate and bromate in drinking water by microcolumn ion chromatography with precolumn enrichment.
(14/58)
A selective and simple method for the determination of iodate (IO3-) and bromate (BrO3-) by microcolumn ion chromatography (IC) is presented. In this study, IO3- and BrO3- were determined as IBr2- and tribromide (Br3-), respectively, via a postcolumn reaction with bromide (Br) under acidic conditions with the aid of alpha-cyclodextrin (alpha-CD) in microcolumn IC. IO3- and BrO3- were selectively detected by the present method at a wavelength of 253 or 265 nm. The present system achieved good selectivity for IO3- and BrO3- as well as good repeatability under suitable conditions. Precolumn enrichment improved the detection limit, and allowed the determination of BrO3- in bottled water as low as sub microg L(-1) level in microcolumn IC. (+info)
Kinetic determination of thiocyanate on the basis of its catalytic effect on the oxidation of methylene blue with potassium bromate.
(15/58)
This study reports a sensitive kinetic spectrophotometric method for the determination of trace amounts of thiocyanate. In acidic solution, Methylene Blue (MB) is oxidized by bromate to form a colorless compound. The reaction is accelerated by trace amounts of thiocyanate and can be followed by measuring the absorbance at 664 nm. The absorbance of the reaction decreased with an increase in the reaction time. Under the optimum experimental conditions (0.56 M of sulfuric acid, 3.9 x 10(-5) M of MB, 3.0 x 10(-3) M of bromate, 180 s, 25 degrees C), thiocyanate can be determined in the range 5.0 - 180 ng/ml. The relative standard deviations (n = 8) are 2.81 and 1.43% for 10.0 and 150 ng/ml thiocyanate, respectively. The detection limit of this method is (3sigma) 3.8 ng/ml. This method was successfully applied to the determination of thiocyanate in real samples. (+info)
An elderly patient with severe acute renal failure due to sodium bromate intoxication.
(16/58)
Accidental or deliberate ingestion of bromate solution has been reported in pediatric as well as adult cases; however there have been no reports of such intoxication in the elderly. We report a 78-year-old woman who suffered severe acute renal failure due to the accidental ingestion of sodium bromate solution. The patient was successfully treated with hemodialysis therapy and renal function recovered without hearing loss. This case suggests that emergency therapeutic measures, including hemodialysis, should be taken as soon as possible, and the rapid removal of bromate is essential to prevent severe intoxication and its sequelae. To the best of our knowledge this is the first report of an elderly patient that demonstrates the clinical benefit of hemodialysis therapy for bromate intoxication. (+info)