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Original Article

Korean J Physiol Pharmacol 2016; 20(1): 15-23

Published online January 1, 2016 https://doi.org/10.4196/kjpp.2016.20.1.15

Copyright © Korean J Physiol Pharmacol.

Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Qi Guo1, Zhiyang Shen1, Hongxia Yu1, Gaofeng Lu2, Yong Yu2, Xia Liu2, and Pengyuan Zheng2,*

Departments of 1Ultrasound, 2Gastroenterology, The Second Hospital Aἀliated of Zhengzhou University, Zhengzhou, Henan 450014, P. R. China

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IκBα and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Keywords: Acetaminophen, Anti-oxidation, Carnosic acid, Hepatotoxicity, Nuclear factor erythroid 2-related factor 2