Trichloroethylene injures rat liver and elevates the level of peroxisomal bifunctional enzyme (Ehhadh)

[摘要] 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.

[关键词] Trichloroethylene;Peroxisomal bifunctional enzyme;Dose-dependent manner;Difference gel electrophoresis (DIGE);MALDI-TOF MS/MS