title: NMR-based metabonomic and quantitative real-time PCR in the profiling of metabolic changes in carbon tetrachloride-induced rat liver injury.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi, PR China. Electronic address: ample1007@sxu.edu.cn.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Dongqin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi, PR China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi, PR China. Electronic address: qinxm@sxu.edu.cn.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Qin
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi, PR China; Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000975:Antioxidants; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Acute liver injury; CCl(4); Metabonomics; Quantitative real-time PCR; System metabolic responses