Comparison of therapeutic effects between topical 8-oxo-2′-deoxyguanosine and corticosteroid in ocular alkali burn model

• Published in: Scientific reports Vol. 11; no. 1; pp. 6909 - 11
• Main Authors: Kim, Dong Hyun, Im, Sang-Taek, Yoon, Jin Young, Kim, Seunghoon, Kim, Mee Kum, Chung, Myung-Hee, Park, Chul-Kyu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/2778; 692/699/3161; 8-Hydroxy-2'-Deoxyguanosine - therapeutic use; Acetic acid; Administration, Ophthalmic; Animals; Burns, Chemical - drug therapy; Cornea; Corneal Injuries - drug therapy; Corticosteroids; Deoxyguanosine; Drug Evaluation, Preclinical; Elastase; Eye Burns - chemically induced; Female; Fluorometholone - therapeutic use; Glucocorticoids - therapeutic use; Humanities and Social Sciences; Inflammation; Interleukin 6; Leukocytes (neutrophilic); Mice; Mice, Inbred BALB C; multidisciplinary; NAD(P)H oxidase; NADPH-diaphorase; Prednisolone; Reactive nitrogen species; Reactive oxygen species; Science; Science (multidisciplinary); Sodium Hydroxide; Steroids; Transcription; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-86440-7

We compared the therapeutic effects of topical 8-oxo-2′-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p  < 0.01). The numbers of cells stained for neutrophil elastase and F4/80-positive inflammatory cells were significantly decreased, with levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and total ROS/RNS amounts markedly reduced in the 8-oxo-dG, FML, and PDE groups (each p  < 0.05). Levels of NADPH oxidase type 2 and 4 were substantially more repressed in the 8-oxo-dG-treated group than in the PDE-treated group (each p  < 0.05). Topical 8-oxo-dG showed excellent therapeutic effects that were comparable with those treated with topical PDE in a murine ocular alkali burn model.