title: Protective effects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes.
abstract: Increasing evidence regarding free radical generating agents and the inflammatory process suggest that accumulation of reactive oxygen species (ROS) could involve hepatotoxicity. Hesperidin, a naturally occurring flavonoid presents in fruits and vegetables, has been reported to exert a wide range of pharmacological effects that include antioxidant, anti-inflammatory, antihypercholesterolemic, and anticarcinogenic actions. However, the cytoprotection and mechanism of hesperidin to neutralize oxidative stress in human hepatic L02 cells remain unclear. In this work, we assessed the capability of hesperidin to prevent tert-butyl hydroperoxide (t-BuOOH)-induced cell damage by augmenting cellular antioxidant defense. Hesperidin significantly protected hepatocytes against t-BuOOH-induced cell cytotoxicity, such as mitochondrial membrane potential (MMP) deplete and lactate dehydrogenase (LDH) release. Hesperidin also remarkably prevented indicators of oxidative stress, such as the ROS and lipid peroxidation level in a dose-dependent manner. Western blot showed that hesperidin facilitated ERK/MAPK phosphorylation which appeared to be responsible for nuclear translocation of Nrf2, thereby inducing cytoprotective heme oxygenase-1 (HO-1) expression. Based on the results described above, it suggested that hesperidin has potential as a therapeutic agent in the treatment of oxidative stress-related hepatocytes injury and liver dysfunctions.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, China.
authors.forename: Mingcang
authors.initials: M
authors.lastname: Chen
authors.forename: Honggang
authors.initials: H
authors.lastname: Gu
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Ye
authors.forename: Bing
authors.initials: B
authors.lastname: Lin
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Weiping
authors.initials: W
authors.lastname: Deng
authors.forename: Jingzhe
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000975:Antioxidants; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020011:Protective Agents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D006569:Hesperidin; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases