Hua Yang1, Tingshu Jiang2, Ping Li1, Qishan Mao2. 1. Respiratory Department, Yantai Hospital of Traditional Chinese Medicine, Xingfu Road No.39, Zhifu District, Yantai City, Shandong Province, China. 2. Respiratory Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University; Yuhuangding East Road No.20, Zhifu District, Yantai City, Shandong Province, China.
Abstract
BACKGROUND: Acetaminophen (APAP)-induced liver toxicity remains the key factor limiting the clinical application of APAP, and herbs are the important sources for isolation of compounds preventing APAP-induced toxicity. AIMS: To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method. METHODS: APAP-induced liver toxicity model was made through intraperitoneal injection (i.p.) of APAP (400 mg/kg). Glycyrrhetinic acid was dissolved in corn oil, and intraperitoneal injection (i.p.) of glycyrrhetinic acid (500 mg/kg body weight) was performed for 20 days before the injection of APAP. UPLC-ESI-QTOF MS was employed to analyze the metabolomic profile of serum samples. RESULTS: The pre-treatment of glycyrrhetinic acid significantly protected APAP-induced toxicity, indicated by the histology of liver, the activity of ALT and AST. Metabolomics showed that the level of palmtioylcarnitine and oleoylcarnitine significantly increased in serum of APAP-treated mice, and the pre-treatment with GA can prevent this elevation of these two fatty acid-carnitines. CONCLUSION: Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity.
BACKGROUND:Acetaminophen (APAP)-induced liver toxicity remains the key factor limiting the clinical application of APAP, and herbs are the important sources for isolation of compounds preventing APAP-induced toxicity. AIMS: To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method. METHODS:APAP-induced liver toxicity model was made through intraperitoneal injection (i.p.) of APAP (400 mg/kg). Glycyrrhetinic acid was dissolved in corn oil, and intraperitoneal injection (i.p.) of glycyrrhetinic acid (500 mg/kg body weight) was performed for 20 days before the injection of APAP. UPLC-ESI-QTOF MS was employed to analyze the metabolomic profile of serum samples. RESULTS: The pre-treatment of glycyrrhetinic acid significantly protected APAP-induced toxicity, indicated by the histology of liver, the activity of ALT and AST. Metabolomics showed that the level of palmtioylcarnitine and oleoylcarnitine significantly increased in serum of APAP-treated mice, and the pre-treatment with GA can prevent this elevation of these two fatty acid-carnitines. CONCLUSION: Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity.
Authors: Andrew D Patterson; Yatrik M Shah; Tsutomu Matsubara; Kristopher W Krausz; Frank J Gonzalez Journal: Hepatology Date: 2012-06-06 Impact factor: 17.425
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