Lupeol protects against acetaminophen-induced oxidative stress and cell death in rat primary hepatocytes
- 作者：Archana Kumari ; Poonam Kakkar ; pkakkar@iitr.res.in ; poonam_kakkar@yahoo.com
- 关键词：AAP ; acetaminophen ; DCFHDA ; 2&prime ; 7&prime ; -dichlorofluorescein-diacetate ; JC-1 ; 5 ; 5&prime ; 6 ; 6&prime ; -Tetrachloro-1 ; 1&prime ; 3 ; 3&prime ; -tetraethyl benzimidazolyl carbocyanine iodide ; PVDF ; polyvinylidene fluoride ; GSH ; reduced glutathione ; GSSG ; oxidiz
- 刊名：Food and Chemical Toxicology
- 出版年：2012
- 期刊代码：20_02786915
- 类别：pha
- 出版时间：May, 2012
- 卷：50
- 期：5
- 页码：1781-1789
- 文件大小：1170 K
摘要
Drug induced hepatotoxicity is a major problem where phytochemicals hold promise for its abrogation. This study was carried out to explore cytoprotective potential of lupeol, a triterpene, against acetaminophen (AAP)-induced toxicity in rat hepatocytes. AAP exposure significantly (p < 0.05) reduced cell viability, disturbed Bcl-2 family pro/anti-apoptotic protein balance, increased ROS production and altered redox homeostasis. It also induced mitochondria-mediated hepatocellular injury by significant mitochondrial depolarization, caspase-9/3 activation and subsequent DNA fragmentation. Our results suggest that lupeol pre-treatment effectively restored antioxidant enzyme levels, decreased lipid peroxidation, inhibited ROS generation and depolarization of mitochondria. Lupeol also attenuated mitochondria-mediated signaling pathway and DNA damage as evident from TUNEL assay and cell cycle studies leading to prevention of cytotoxicity. This study confirms the efficacy of lupeol, a food derived antioxidant, in abrogating ROS generation, maintaining redox balance and providing significant protection against mitochondria-mediated cell death during AAP-induced toxicity.