Lupeol protects against acetaminophen-induced oxidative stress and cell death in rat primary hepatocytes |
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Authors: | Archana Kumari Poonam Kakkar |
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Affiliation: | Herbal Research Section, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, 226001 Lucknow, India |
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Abstract: | 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. |
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Keywords: | 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, oxidized glutathione HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid LPO, lipid peroxidation MDA, malondialdehyde MFI, mean fluorescence intensity MPT, mitochondrial membrane permeability transition MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide NBT, nitroblue tetrazolium ROS, reactive oxygen species TBA, thiobarbituric acid SOD, superoxide dismutase TBARS, thiobarbituric acid reactive substances t-BHP, tert-butyl hydroperoxide TCA, trichloroacetic acid ΔΨm, mitochondrial membrane potential |
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