Background

Trichloroethylene (TCE) is a common industrial solvent and an occupational toxicant. TCE exposure can cause severe hepatotoxicity, but its mode of action is poorly understood. Many studies have shown TCE-induced liver damage in mice, while few have examined the effects of TCE in rats.

Objective

To explore the effects of TCE in Sprague–Dawley (SD) rats and the potential mechanisms in TCE-induced hepatocytotoxicity.

Results

The liver index and activities of liver damage marker enzymes (ALT, AST and ALP) in rat serum were elevated along with the increase in TCE dose, while the levels of total proteins and albumin in serum were reduced. The results suggest that TCE is hepatotoxic in rats. 2D-DIGE electrophoresis showed that the levels of 66 liver proteins in TCE-treated rats were abnormally altered (39 up-regulated and 27 down-regulated). In these proteins, six enzymes were related to liver damage and carcinogenesis as indicated by bioinformatics analysis, and Western blot analysis confirmed the alterations of three of them, i.e., aldehyde dehydrogenase 2 (Aldh2), glutathione S-transferase Mu 1 (Gstm1) and peroxisomal bifunctional enzyme (PBE, also named as Ehhadh). PBE was the only protein elevated in a dose dependent manner. Whether PBE can be a biomarker of TCE hepatotoxicity needs to be further studied.

Conclusion

These findings indicate that TCE induces liver injury in rats.

中文翻译：

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三氯乙烯损伤大鼠肝脏并提高过氧化物酶体双功能酶（Ehhadh）的水平

背景

三氯乙烯（TCE）是一种常见的工业溶剂和职业性毒物。TCE暴露可引起严重的肝毒性，但对其作用方式了解甚少。许多研究表明，TCE引起的小鼠肝损伤，而很少研究TCE对大鼠的影响。

目的

探讨TCE对Sprague-Dawley（SD）大鼠的影响以及TCE诱导的肝细胞毒性的潜在机制。

结果

随着TCE剂量的增加，大鼠血清中的肝指数和肝损伤标记酶（ALT，AST和ALP）的活性升高，而血清中总蛋白和白蛋白的水平降低。结果表明TCE在大鼠中具有肝毒性。2D-DIGE电泳显示，经TCE处理的大鼠中66种肝蛋白水平异常改变（上调39种，下调27种）。如生物信息学分析所示，在这些蛋白质中，六种酶与肝损伤和癌变有关，蛋白质印迹分析证实了其中三种的改变，即醛脱氢酶2（Aldh2），谷胱甘肽S-转移酶Mu 1（Gstm1）和过氧化物酶体双功能酶（PBE，也称为Ehhadh）。PBE是唯一以剂量依赖性方式升高的蛋白质。

结论

这些发现表明TCE诱导大鼠肝损伤。