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

Qi Guo; Zhiyang Shen; Hongxia Yu; Gaofeng Lu; Yong Yu; Xia Liu; Pengyuan Zheng

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자료유형: 학술저널

저자정보: Qi Guo (The Second Hospital Affiliated of Zhengzhou University) Zhiyang Shen (The Second Hospital Affiliated of Zhengzhou University) Hongxia Yu (The Second Hospital Affiliated of Zhengzhou University) Gaofeng Lu (The Second Hospital Affiliated of Zhengzhou University) Yong Yu (The Second Hospital Affiliated of Zhengzhou University) Xia Liu (The Second Hospital Affiliated of Zhengzhou University) Pengyuan Zheng (The Second Hospital Affiliated of Zhengzhou University)

저널정보: 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제20권 제1호

발행연도: 2016.1

수록면: 15 - 23 (9page)

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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-a, IL-1b, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IkBa 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.

#Acetaminophen #Anti-oxidation #Carnosic acid #Hepatotoxicity #Nuclear factor erythroid 2-related factor 2

참고문헌 (33)

참고문헌 신청

Bernal W / 2010 / Acute liver failure / Lancet 376:190~201

Blieden M / 2014 / A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States / Expert Rev Clin Pharmacol 7:341~348

Mitka M. / 2014 / FDA asks physicians to stop prescribing high-dose acetaminophen products / JAMA 311:563

Holubek WJ / 2006 / Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study / Hepatology 43:880

Jaeschke H / 2011 / Current issues with acetaminophen hepatotoxicity--a clinically relevant model to test the efficacy of natural products / Life Sci 88:737~745

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