title: Edaravone protects against hyperosmolarity-induced oxidative stress and apoptosis in primary human corneal epithelial cells.
abstract: An increase in the osmolarity of tears induced by excessive evaporation of the aqueous tear phase is a major pathological mechanism behind dry eye. Exposure of epithelial cells on the surface of the human eye to hyperosmolarity leads to oxidative stress, mitochondrial dysfunction, and apoptosis. Edaravone, a hydroxyl radical scavenging agent, is clinically used to reduce neuronal damage following ischemic stroke. In this study, we found that treatment with hyperosmotic media at 400 and 450 mOsM increased the levels of ROS and mitochondrial oxidative damage, which were ameliorated by edaravone treatment in a dose-dependent manner. We also found that edaravone could improve mitochondrial function in HCEpiCs by increasing the levels of ATP and mitochondrial membrane potential. MTT and LDH assays indicated that edaravone could attenuate hyperosmolarity-induced cell death. It was found that edaravone prevented apoptosis by decreasing the level of cleaved caspase-3, and attenuating the release of cytochrome C. Mechanistically, we found that edaravone augmented the expression of Nrf2 and its target genes, such as HO-1, GPx-1, and GCLC.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D000077553:Edaravone; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D020011:Protective Agents; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D053148:Caspase 3; D000077553:Edaravone; D000983:Antipyrine