Abstract
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. To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method. 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. 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. Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity.
Highlights
The human respiratory system is divided into the upperCorresponding author: Hua Yang, Respiratory Department, Yantai Hospital of Traditional Chinese Medicine, Xingfu Road No.[39], Zhifu District,Yantai City, Shandong Province, ChinaThe adverse effects of acetaminophen (APAP) remain the major reason in limiting the clinical application of APAP which is one of the most important over-thecounter analgesic and antipyretic drugs
Given that the disruption of fatty acids metabolism is an important reason for APAP-induced toxicity, the present study aimed to investigate the influence of glycyrrhetinic acid towards acetaminophen (APAP)-induced fatty acids metabolism
APAP-induced liver toxicity model was made through intraperitoneal injection (i.p.) of APAP (400 mg/kg)
Summary
The human respiratory system is divided into the upperCorresponding author: Hua Yang, Respiratory Department, Yantai Hospital of Traditional Chinese Medicine, Xingfu Road No.[39], Zhifu District,Yantai City, Shandong Province, ChinaThe adverse effects of acetaminophen (APAP) remain the major reason in limiting the clinical application of APAP which is one of the most important over-thecounter analgesic and antipyretic drugs. Given that the disruption of fatty acids metabolism is an important reason for APAP-induced toxicity, the present study aimed to investigate the influence of glycyrrhetinic acid towards acetaminophen (APAP)-induced fatty acids metabolism. 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. 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
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