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六价铬在体内产生自由基:电子自旋共振自旋捕获研究

In vivo free radical generation by chromium(VI): an electron spin resonance spin-trapping investigation.

作者信息

Kadiiska M B, Xiang Q H, Mason R P

机构信息

Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.

出版信息

Chem Res Toxicol. 1994 Nov-Dec;7(6):800-5. doi: 10.1021/tx00042a013.

Abstract

Although studies in chemical and biological systems have demonstrated that free radical formation is mediated by Cr(VI), no ESR evidence for the generation of free radicals in vivo has been reported. We have employed an ESR spin-trapping technique to detect an adduct of the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) in the bile of animals given an intragastric dose of potassium dichromate. In this study, we provide evidence for in vivo radical generation resulting from Cr(VI)-poisoned rats. Upon the administration of Cr(VI) and 4-POBN, the ESR spectrum of the radical adducts present in the bile exhibited hyperfine coupling constants aN = 15.71 G and a beta H = 2.90 G. We suggest that the radical responsible for this 4-POBN adduct is carbon-centered and derived from endogenous lipids. The radical adducts detected in the bile from Cr(VI)-treated rats are proposed to be formed and trapped in the liver and excreted into bile. This is the first report of electron spin resonance evidence for the in vivo generation of free radicals by Cr(VI).

摘要

尽管在化学和生物系统中的研究表明,自由基的形成是由六价铬介导的,但尚未有关于体内自由基生成的电子顺磁共振(ESR)证据的报道。我们采用ESR自旋捕获技术,在给动物灌胃重铬酸钾后,检测其胆汁中自旋捕获剂α-(4-吡啶基1-氧化物)-N-叔丁基硝酮(4-POBN)的加合物。在本研究中,我们提供了六价铬中毒大鼠体内自由基生成的证据。给予六价铬和4-POBN后,胆汁中存在的自由基加合物的ESR谱显示超精细偶合常数aN = 15.71 G和aβH = 2.90 G。我们认为,这种4-POBN加合物的自由基是以碳为中心的,来源于内源性脂质。在六价铬处理大鼠的胆汁中检测到的自由基加合物被认为是在肝脏中形成并捕获,然后排泄到胆汁中。这是关于六价铬在体内生成自由基的电子自旋共振证据的首次报道。

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