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Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice
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.
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Full text: 1 Index: WPRIM Main subject: Aspartate Aminotransferases / RNA, Messenger / Blotting, Western / Cytokines / Interleukin-6 / Tumor Necrosis Factor-alpha / Reactive Oxygen Species / Liver Failure, Acute / Hepatocytes / Alanine Transaminase Limits: Animals Language: En Journal: The Korean Journal of Physiology and Pharmacology Year: 2016 Type: Article
Full text: 1 Index: WPRIM Main subject: Aspartate Aminotransferases / RNA, Messenger / Blotting, Western / Cytokines / Interleukin-6 / Tumor Necrosis Factor-alpha / Reactive Oxygen Species / Liver Failure, Acute / Hepatocytes / Alanine Transaminase Limits: Animals Language: En Journal: The Korean Journal of Physiology and Pharmacology Year: 2016 Type: Article