title: The protection of glycyrrhetinic acid (GA) towards acetaminophen (APAP)-induced toxicity partially through fatty acids metabolic pathway.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity.
authors.affiliation: Respiratory Department, Yantai Hospital of Traditional Chinese Medicine, Xingfu Road No.39, Zhifu District, Yantai City, Shandong Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Respiratory Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University; Yuhuangding East Road No.20, Zhifu District, Yantai City, Shandong Province, China.
authors.forename: Tingshu
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Respiratory Department, Yantai Hospital of Traditional Chinese Medicine, Xingfu Road No.39, Zhifu District, Yantai City, Shandong Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Respiratory Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University; Yuhuangding East Road No.20, Zhifu District, Yantai City, Shandong Province, China.
authors.forename: Qishan
authors.initials: Q
authors.lastname: Mao
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL
chemical_list: D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006034:Glycyrrhetinic Acid
keywords: Glycyrrhetinic acid (GA); acetaminophen (APAP); fatty acid; metabolomics