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. 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.