Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi, PR China; College of Chemistry and Chemical Engineering, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi, PR China.
Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi, PR China.
J Pharm Biomed Anal. 2014 Feb;89:42-9. doi: 10.1016/j.jpba.2013.10.023. Epub 2013 Oct 28.
Carbon tetrachloride (CCl4) is commonly used as a model toxicant to induce chronic and acute liver injuries. In this study, metabolite profiling and gene expression analysis of liver tissues were performed by nuclear magnetic resonance and quantitative real-time polymerase chain reaction to understand the responses of acute liver injury system in rats to CCl4. Acute liver injury was successfully induced by CCl4 as revealed by histopathological results and significant increase in alanine aminotransferase and serum aspartate aminotransferase. We found that CCl4 caused a significant increase in lactate, succinate, citrate, dimethylgycine, choline and taurine. CCl4 also caused a decrease in some of the amino acids such as leucine/isoleucine, glutamine/glutathione and betaine. Gene function analysis revealed that 10 relevant enzyme genes exhibited changes in expressions in the acute liver injury model. In conclusion, the metabolic pathways, including tricarboxylic acid cycle, antioxidant defense systems, fatty acid β-oxidation, glycolysis and choline and mevalonate metabolisms were impaired in CCl4-treated rat livers. These findings provided an overview of the biochemical consequences of CCl4 exposure and comprehensive insights into the metabolic aspects of CCl4-induced hepatotoxicity in rats. These findings may also provide reference of the mechanisms of acute liver injury that could be used to study the changes in functional genes and metabolites.
四氯化碳（CCl4）常被用作诱导慢性和急性肝损伤的模型毒物。在这项研究中，通过核磁共振和定量实时聚合酶链反应对肝组织进行代谢物谱分析和基因表达分析，以了解 CCl4 诱导的大鼠急性肝损伤系统的反应。肝组织病理学结果和丙氨酸氨基转移酶和血清天冬氨酸氨基转移酶的显著增加表明急性肝损伤成功诱导。我们发现 CCl4 导致乳酸、琥珀酸、柠檬酸、二甲甘氨酸、胆碱和牛磺酸显著增加。CCl4 还导致一些氨基酸如亮氨酸/异亮氨酸、谷氨酰胺/谷胱甘肽和甜菜碱减少。基因功能分析显示，10 个相关酶基因在急性肝损伤模型中的表达发生变化。总之，CCl4 处理的大鼠肝脏中的三羧酸循环、抗氧化防御系统、脂肪酸β-氧化、糖酵解和胆碱及甲羟戊酸代谢等代谢途径受到损害。这些发现提供了 CCl4 暴露的生化后果的概述，并全面了解了 CCl4 诱导的大鼠肝毒性的代谢方面。这些发现还可能为急性肝损伤的机制提供参考，可以用于研究功能基因和代谢物的变化。
