Liu Fangping, Lin Yuexia, Li Zhi, Ma Xin, Han Qing, Liu Yingshu, Zhou Qiong, Liu Jingli, Li Rui, Li Jichang, Gao Li
College of Veterinary Medicine, Northeast Agricultural University, Harbin, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, PR China.
Food Chem Toxicol. 2014 Sep;71:225-30. doi: 10.1016/j.fct.2014.06.011. Epub 2014 Jun 22.
Three acute hepatic injury models (a CCl4-induced model, APAP-induced model and ethanol-induced model) in mice were used to study the importance of GSTA1 in acute hepatic injury by comparison with a standard enzyme marker, alanine aminotransferase (ALT). GSTA1 release was demonstrated to be an earlier and more sensitive indicator of hepatotoxicity than was ALT. Significant increases in GSTA1 were detected at 2 h after CCl4 exposure, while ALT was undetected at this time. GSTA1 was also a more sensitive indicator of hepatotoxicity than ALT after 6 h. In the APAP and ethanol models, GSTA1 was markedly increased earlier than ALT, at 2 h post exposure. The release of GSTA1 was significantly increased at a dose of 12.5 mg/kg (CCl4 model), 100 mg/kg (APAP model) and 10 ml/kg (ethanol model), the lowest exposure concentration for each model. In contrast, AST release was not statistically significant. These results suggest that GSTA1 can be detected at low concentrations during the early stages of acute hepatic injury and that GSTA1 is a more sensitive and more accurate indicator than ALT.
利用小鼠的三种急性肝损伤模型（四氯化碳诱导模型、对乙酰氨基酚诱导模型和乙醇诱导模型），通过与标准酶标志物丙氨酸转氨酶（ALT）比较，研究谷胱甘肽S-转移酶A1（GSTA1）在急性肝损伤中的重要性。结果表明，与ALT相比，GSTA1释放是肝毒性更早且更敏感的指标。四氯化碳暴露后2小时检测到GSTA1显著增加，而此时未检测到ALT。6小时后，GSTA1也是比ALT更敏感的肝毒性指标。在对乙酰氨基酚和乙醇模型中，暴露后2小时GSTA1比ALT更早显著增加。在12.5 mg/kg（四氯化碳模型）、100 mg/kg（对乙酰氨基酚模型）和10 ml/kg（乙醇模型）剂量下，即每个模型的最低暴露浓度时，GSTA1释放显著增加。相比之下，天冬氨酸转氨酶（AST）释放无统计学意义。这些结果表明，在急性肝损伤早期低浓度时即可检测到GSTA1，且GSTA1是比ALT更敏感、更准确的指标。
