Hepatoprotective effects of berberine on acetaminophen-induced hepatotoxicity in mice - 29/05/18
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Graphical abstract |
Highlights |
• | BBR pretreatment protects against APAP hepatotoxicity. |
• | BBR pretreatment fails to ameliorate APAP-induced GSH depletion. |
• | BBR activates Nrf-2/Mn-SOD antioxidative signaling pathway. |
• | BBR prevents APAP-induced DNA fragmentation. |
• | BBR inhibits activation of NF-κB and inflammasome during APAP hepatotoxicity. |
Abstract |
Acetaminophen (APAP) hepatotoxicity remains the leading cause of drug-induced liver injury due to the lack of safe and effective therapeutic agents. Berberine (BBR) is a natural alkaloid derived from traditional medicine Rhizoma Coptidis and possesses various pharmacological properties. The aim of this study was to explore the hepatoprotective effects and underlying mechanisms of BBR on APAP-induced hepatotoxicity. Our results indicated that BBR pretreatment significantly ameliorated APAP-induced hepatic pathological abnormalities and attenuated the elevations of serum aminotransferases and liver/body weight ratio. Compared to APAP group, BBR notably increased the levels of hepatic UDP-glucuronosyltransferases and sulfotransferases, whereas failed to ameliorate APAP-induced GSH depletion. Pretreatment with BBR significantly reduced hepatic MDA and MPO levels, inhibited JNK phosphorylation and up-regulated the expression of nuclear Nrf-2 and its downstream gene Mn-SOD. Additionally, BBR obviously prevented APAP-induced DNA fragmentation. Furthermore, BBR pretreatment dramatically reduced the expression of pro-inflammatory cytokines, HMGB1, p-p65 and cleaved caspase-1 and inhibited the infiltration of macrophages and neutrophils. Taken these results together, BBR exhibits notable preventive effects on APAP-induced hepatotoxicity by inhibiting oxidative stress, hepatocyte necrosis and inflammatory response.
Le texte complet de cet article est disponible en PDF.Abbreviations : APAP, BBR, UGTs, SULTs, CYP2E1, NAPQI, GSH, ROS, JNK, HMGB1, DAMPs, PRRs, NF-κB, NAC, ALT, AST, MDA, MPO, Nrf2
Keywords : Berberine, Acetaminophen, Hepatotoxicity, Metabolism, Oxidative stress, Inflammation
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Vol 103
P. 1319-1326 - juillet 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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