ROLE OF METALLOTHIONEIN IN ZINC(II) AND CHROMIUM(III) MEDIATED TOLERANCE TO CARBON-TETRACHLORIDE HEPATOTOXICITY - EVIDENCE AGAINST A TRICHLOROMETHYL RADICAL-SCAVENGING MECHANISM
ROLE OF METALLOTHIONEIN IN ZINC(II) AND CHROMIUM(III) MEDIATED TOLERANCE TO CARBON-TETRACHLORIDE HEPATOTOXICITY - EVIDENCE AGAINST A TRICHLOROMETHYL RADICAL-SCAVENGING MECHANISM
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DOI：
10.1021/tx00035a017
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发表时间：
1993-09-01
影响因子：
4.1
通讯作者：
MASON, RP
中科院分区：
文献类型：
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作者：
HANNA, PM;KADIISKA, MB;MASON, RP
CCl 4代谢过程中产生的.CCl3自由基在体内和体外容易被苯基N-叔丁基硝酮（PBN）自旋捕获，形成稳定的PBN/.CCl3自由基加合物，然后可以将其萃取到有机溶剂中并通过ESR光谱检测。我们已经使用这种技术来研究锌（II），铬（III），和金属硫蛋白（MT）对四氯化碳在体内毒性的保护作用。肝脏MT，这是由锌（II）诱导，已被提出，以防止四氯化碳诱导的细胞损伤，清除自由基代谢产物形成。四氯化碳诱导的肝毒性显着抑制雄性Sprague-Dawley大鼠预处理与单剂量的5毫克/公斤的锌（II）或铬（III）根据标准血清测定肝脏特异性酶，和肝脏MT升高预处理后与锌（II）或铬（III）。在体外，没有发现任何差异，无论是CCl 4衍生的自由基代谢物形成的量或它们形成的速度从大鼠的微粒体预处理24小时提前5毫克/公斤锌（II）或铬（III）。提取大鼠肝脏与2：1氯仿/甲醇1小时后，给药的0.8 mL/kg的腹腔内或胃内剂量的四氯化碳也显示没有差异的三氯甲基自由基自旋捕获在体内预处理后，无论是锌（II）或铬（III）。这些结果表明，预处理与锌（II）或铬（III）不影响四氯化碳代谢，也没有MT显着抑制三氯甲基自由基代谢物。
The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and detected by ESR spectroscopy. We have used this technique to examine the proposed protective roles of Zn(II), Cr(III), and metallothionein (MT) against carbon tetrachloride toxicity in vivo. Hepatic MT, which is induced by Zn(II), has been proposed to protect against CCl4-induced cellular damage by scavenging the free radical metabolites formed. CCl4-induced hepatotoxicity was significantly suppressed in male Sprague-Dawley rats pretreated with a single dose of 5 mg/kg Zn(II) or Cr(III) according to standard serum assays for liver-specific enzymes, and hepatic MT was elevated after pretreatment with either Zn(II) or Cr(III). In vitro, no difference was detected in either the amount of CCl4-derived free radical metabolites formed or the rate at which they were formed by microsomes from rats pretreated 24 h in advance with 5 mg/kg Zn(II) or Cr(III). Extraction of rat liver with 2:1 chloroform/methanol 1 h after the administration of a 0.8 mL/kg intraperitoneal or intragastric dose of CCl4 also revealed no difference in the amount of trichloromethyl radical spin trapped in vivo following pretreatment with either Zn(II) or Cr(III). These results suggest that pretreatment with either Zn(II) or Cr(III) does not affect CCl4 metabolism nor does the MT significantly scavenge the trichloromethyl free radical metabolite.