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Edaravone Protects Against Hyperosmolarity-induced Oxidative Stress and Apoptosis in Primary Human Corneal Epithelial Cells

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Journal PLoS One
Date 2017 Mar 28
PMID 28346481
Citations 29
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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.

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References
1.
Bai G, Rama Rao K, Murthy C, Panickar K, Jayakumar A, Norenberg M . Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes. J Neurosci Res. 2001; 66(5):981-91. DOI: 10.1002/jnr.10056. View

2.
Luo L, Li D, Pflugfelder S . Hyperosmolarity-induced apoptosis in human corneal epithelial cells is mediated by cytochrome c and MAPK pathways. Cornea. 2007; 26(4):452-60. DOI: 10.1097/ICO.0b013e318030d259. View

3.
Shokrzadeh M, Shaki F, Mohammadi E, Rezagholizadeh N, Ebrahimi F . Edaravone decreases paraquat toxicity in a549 cells and lung isolated mitochondria. Iran J Pharm Res. 2014; 13(2):675-81. PMC: 4157044. View

4.
Choi I, Lee S, Ju C, Nam W, Kim H, Ko K . Protection by a manganese porphyrin of endogenous peroxynitrite-induced death of glial cells via inhibition of mitochondrial transmembrane potential decrease. Glia. 2000; 31(2):155-64. DOI: 10.1002/1098-1136(200008)31:2<155::aid-glia70>3.0.co;2-1. View

5.
Bron A, Yokoi N, Gafney E, Tiffany J . Predicted phenotypes of dry eye: proposed consequences of its natural history. Ocul Surf. 2009; 7(2):78-92. DOI: 10.1016/s1542-0124(12)70299-9. View