Hepatoprotective effects of berberine on acetaminophen-induced hepatotoxicity in mice.

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.

• Authors: Zheng Zhao, Qingyan Wei, Weiwei Hua, Yunxin Liu, Xiang Liu, Yubing Zhu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 103 Pg. 1319-1326 (Jul 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29864914 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Protective Agents
• Berberine
• Acetaminophen

Topics

• Acetaminophen (adverse effects, metabolism)
• Animals
• Berberine (chemistry, pharmacology, therapeutic use)
• Chemical and Drug Induced Liver Injury (drug therapy)
• DNA Fragmentation (drug effects)
• Inflammation (pathology)
• Liver (drug effects, pathology)
• Male
• Mice, Inbred C57BL
• Oxidative Stress (drug effects)
• Protective Agents (chemistry, pharmacology, therapeutic use)