Abstract
Possible prevention and therapeutic intervention strategies to counteract acetaminophen (APAP) hepatotoxicity would be of great value. Wuzhi tablet (WZ, extract of Schisandrae sphenanthera) possesses hepatoprotective effects against hepatitis and the hepatic dysfunction induced by various chemical hepatotoxins. In this study, the protective effect of WZ on APAP-induced hepatic injury was evaluated and targeted metabolomics by LC-MS-based metabolomics was used to examine whether WZ influences hepatic metabolism. The results demonstrated significant hepatoprotection of WZ against APAP-induced liver injury; pretreatment with WZ prior to APAP administration blocks the increase in serum palmitoylcarnitine and oleoylcarnitine and thus restores the APAP-impaired fatty acid β-oxidation to normal levels. These studies further revealed a significant and prolonged upregulation of the PPARα target genes Cpt1 and Acot1 by WZ mainly contributing to the maintenance of normal fatty acid metabolism and thus potentially contributing to the hepatic protection of WZ against APAP-induced hepatic toxicity. Taken together, the current study provides new insights into understanding the hepatoprotective effect of WZ against APAP-induced liver toxicity.
Highlights
Acetaminophen (APAP), known as paracetamol and N-acetyl-p-aminophenol, is the most frequently used and readily available over-the-counter (OTC) analgesic and antipyretic agent in the world
The results demonstrated significant hepatoprotection of WZ against APAP-induced liver injury; pretreatment with WZ prior to APAP administration blocks the increase in serum palmitoylcarnitine and oleoylcarnitine and restores the APAPimpaired fatty acid β-oxidation to normal levels
The present study demonstrates a significant protective effect of Wuzhi tablet (Schisandra Sphenanthera extract) on APAPinduced liver injury, and targeted metabolomics of serum acylcarnitines showed a novel correlation with the hepatoprotective effect of WZ on APAP toxicity
Summary
Acetaminophen (APAP), known as paracetamol and N-acetyl-p-aminophenol, is the most frequently used and readily available over-the-counter (OTC) analgesic and antipyretic agent in the world. It is found in many OTC combination drugs (contained in >100 products) and its use has achieved great popularity, with more than 1 billion tablets sold annually in the United States [1]. Over the past four decades, numerous efforts have been undertaken to elucidate the molecular mechanism of APAP toxicity Some of these mechanisms are well established showing that the toxicity is initiated by accumulation of the toxic reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). A nuclear magnetic resonance- (NMR-) based metabolomics study demonstrated that APAP can cause disruption of carbohydrate and lipid
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