title: Lupeol protects against acetaminophen-induced oxidative stress and cell death in rat primary hepatocytes.
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.
authors.affiliation: Herbal Research Section, CSIR-Indian Institute of Toxicology Research, MG Marg, 226001 Lucknow, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Kumari
authors.forename: Poonam
authors.initials: P
authors.lastname: Kakkar
mesh_terms: D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D005434:Flow Cytometry; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000094042:Lupanes
chemical_list: D000082:Acetaminophen; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; C010480:lupeol; D000094042:Lupanes