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首页> 外文学位 >Differential expression profile of cytochrome p450 2E1 (CYP2E1) related genes associated with carbon tetrachloride-induced hepatotoxicity.
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Differential expression profile of cytochrome p450 2E1 (CYP2E1) related genes associated with carbon tetrachloride-induced hepatotoxicity.

机译：与四氯化碳诱导的肝毒性相关的细胞色素p450 2E1（CYP2E1）相关基因的差异表达谱。

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摘要

The hazardous effects of chemicals are of great concern and widely studied in an effort to determine the mechanisms underlying their toxicity and carcinogenicity. Chemicals such as carbon tetrachloride (CCl4) induce liver injury through free radical mechanism. CCl4 is considered as a prototype for better understanding of free radical-mediated hepatotoxicity. The hepatotoxicity of CCl4 is believed to be mediated by cytochrome P4502E1 (CYP2E1) that belongs to P-450 (P-450s) superfamily of hemoproteins, which carry out oxidative metabolism of many endogenous and xenobiotic chemicals. Definitive proof was obtained from the studies in which CYP2E1 knockout mice were used. It was confirmed that mice, which lack CYP2E1 expression, were resistant to liver damage after i.p. administration of CCl4 (1 ml/kg) for 24 h. In order to extend our understanding on CYP2E1-mediated CCl4 hepatotoxicity, the present study aimed at observing the time-dependent changes that occur at morphological, histopathological, biochemical and molecular levels in both CYP2E1+/+ and CYP2E1-/- mice after treating with either corn oil or CCl4 (1 ml/kg) for 2, 6, 12, 24 and 48 h.; At morphological level, a pale orange colored liver was observed in CYP2E1 +/+ mice treated with CCl4 for 24 and 48 h, while the CYP2E1 +/+ mice treated with corn oil and CYP2E1-/- mice treated with either corn oil or CCl4 showed normal reddish brown color livers. This pale orange color observed in the livers of CYP2E1 +/+ mice was an apparent indication of fatty infiltration resulting from the exposure to CCl4. Ballooned hepatocytes with multiple vacuoles in their cytoplasm, degenerating cells with pyknotic nucleus and collapsed hepatic sinusoids were also observed in the livers of CYP2E1 +/+ mice 24 h after treating with CCl4 and continued till 48 h. Furthermore, the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), markers for liver injury, were significantly higher at 12 h, and were peaked at 24 h with a gradual decrease at 48 h after CCl4 intoxication.; Taken together, our studies at morphological, biochemical, histopathological and molecular levels provided an insight into the CYP2E1-mediated and CCl 4-induced hepatotoxicity, and the genes identified may serve as potential marker genes for understanding the free radical-mediated chemical-induced hepatotoxicity. (Abstract shortened by UMI.)
机译：化学品的有害影响倍受关注，并已广泛研究以确定其毒性和致癌性的潜在机制。四氯化碳（CCl4）等化学物质通过自由基机制诱导肝损伤。 CCl4被认为是更好地了解自由基介导的肝毒性的原型。 CCl4的肝毒性据信是由血色素P-450（P-450s）超家族的细胞色素P4502E1（CYP2E1）介导的，该色素进行许多内源性和异源性化学物质的氧化代谢。从使用CYP2E1基因敲除小鼠的研究中获得了明确的证据。证实缺乏CYP2E1表达的小鼠在腹腔注射后对肝损伤具有抗性。施用CCl4（1 ml / kg）24小时。为了扩展我们对CYP2E1介导的CCl4肝毒性的理解，本研究旨在观察经CYP2E1 + / +和CYP2E1-/-小鼠治疗后随时间变化的形态，组织病理学，生化和分子水平玉米油或CCl4（1 ml / kg）持续2、6、12、24和48小时。在形态学水平上，经CCl4处理的CYP2E1 + / +小鼠在24和48 h观察到淡橙色肝脏，而用玉米油处理的CYP2E1 + / +小鼠和用玉米油或CCl4处理的CYP2E1-/-小鼠观察到显示正常的红棕色肝脏。在CYP2E1 + / +小鼠的肝脏中观察到的淡橙色明显是由于暴露于CCl4引起的脂肪浸润。 CYP2E1 + / +小鼠肝脏经CCl4处理后24 h并持续至48 h，在其细胞质中具有多个液泡的气球状肝细胞，具有致死性核的变性细胞和塌陷的肝窦结构也被观察到。此外，肝损伤的标志物血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平在12 h时显着升高，并在24 h达到峰值，在CCl4中毒后48 h逐渐下降。综上所述，我们在形态，生化，组织病理学和分子水平上的研究提供了对CYP2E1介导和CCl 4诱导的肝毒性的认识，并且鉴定出的基因可能是潜在的标记基因，可用于理解自由基介导的化学诱导的肝毒性。 （摘要由UMI缩短。）

著录项

  • 作者

    Sreedevi, Avasarala.;

  • 作者单位

    The Chinese University of Hong Kong (People's Republic of China).;

  • 授予单位 The Chinese University of Hong Kong (People's Republic of China).;
  • 学科 Health Sciences Toxicology.; Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 377 p.
  • 总页数 377
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学（毒理学）;生物化学;
  • 关键词

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