An in vivo ESR spin-trapping study: free radical generation in rats from formate intoxication--role of the Fenton reaction.

Dikalova AE; Kadiiska MB; Mason RP

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An in vivo ESR spin-trapping study: free radical generation in rats from formate intoxication--role of the Fenton reaction.

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Electron spin resonance spectroscopy has been used to study free radical generation in rats with acute sodium formate poisoning. The in vivo spin-trapping technique was used with alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN), which reacts with free radical metabolites to form radical adducts, which were detected in the bile and urine samples from Fischer rats. The use of (13)C-sodium formate and computer simulations of the spectra identified the 12-line spectrum as arising from the POBN/carbon dioxide anion radical adduct. The identification of POBN/*CO(2)(-) radical adduct provides direct electron spin resonance spectroscopy evidence for the formation of *CO(2)(-) radicals during acute intoxication by sodium formate, suggesting a free radical metabolic pathway. To study the mechanism of free radical generation by formate, we tested several known inhibitors. Both allopurinol, an inhibitor of xanthine oxidase, and aminobenzotriazole, a cytochrome P450 inhibitor, decreased free radical formation from formate, which may imply a dependence on hydrogen peroxide. In accord with this hypothesis, the catalase inhibitor 3-aminotriazole caused a significant increase in free radical formation. The iron chelator Desferal decreased the formation of free radicals up to 2-fold. Presumably, iron plays a role in the mechanism of free radical generation by formate via the Fenton reaction. The detection of formate free radical metabolites generated in vivo and the key role of the Fenton reaction in this process may be important for understanding the pathogenesis of both formate and methanol intoxication.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2001年第24期|13549-13553|共5页
作者
Dikalova AE; Kadiiska MB; Mason RP;
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作者单位

Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.;

opcsi.unian.it;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Carbon Dioxide; Formic Acids; Free Radicals; Iron; 二氧化碳; 甲酸类; 自由基; 铁;

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An in vivo ESR spin-trapping study: free radical generation in rats from formate intoxication--role of the Fenton reaction.

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