Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice
The Korean Journal of Physiology and Pharmacology
; : 15-23, 2016.
Article
in En
| WPRIM
| ID: wpr-727998
Responsible library:
WPRO
ABSTRACT
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-alpha, IL-1beta, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IkappaBalpha 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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Aspartate Aminotransferases
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RNA, Messenger
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Blotting, Western
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Cytokines
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Interleukin-6
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Tumor Necrosis Factor-alpha
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Reactive Oxygen Species
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Liver Failure, Acute
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Hepatocytes
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Alanine Transaminase
Limits:
Animals
Language:
En
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2016
Type:
Article