Metabolomics evaluation of the effects of green tea extract on acetaminophen-induced hepatotoxicity in mice

Green tea has a considerable amount of polyphenolic catechins and has been promoted to have beneficial effects on health including protective effects against oxidative stress.Acetaminophen(APAP) is a widely used analgesic drug which is usually safe at recommended therapeutic doses but overdose can cause acute liver injury.These studies explored the effects of green tea extract(GTE) on APAP-induced hepatotoxicity using UPLC /MS-and NMR-based metabolomic approaches.Male B6C3F1 mice were orally administered GTE under three scenarios either prior to or after a single dose of APAP.UPLC /MS and NMR were employed for metabolomics analysis of the biochemical changes in mice livers with GTE pretreatment 3 h or 3 d prior to APAP exposure or GTE exposure 6 h after APAP.Based upon the data,GTE given prior to APAP ameliorated the APAP-induced hepatotoxicity in a dose dependent manner whereas GTE given after APAP potentiated the toxicity.Metabolites belonging to multiple classes including but not limited to acylcarnitines,energy metabolism,bile acids,and lysoPCs were identified and semi-quantified.These metabolites were significantly altered by APAP exposure alone compared to control.GTE pretreatment generally resulted in these metabolite levels returning to control levels or being less altered.GTE given after APAP,however,caused more changes in the metabolites over what was induced by APAP alone indicating more severe hepatotoxicity.Combined with biochemistry and histopathology results,the changes in liver metabolites indicated perturbations of fatty acid metabolism,energy metabolism,bile acids metabolism and phospholipids metabolism induced by APAP with differing effects on these metabolites depending upon the time of GTE exposure.The results indicate that the time at which GTE was given highly influenced the severity of APAPinduced toxicity.These studies clearly highlight the need to understand the interactions between herbs and other dietary supplements with commonly used over-the-counter or prescription drugs.