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Neuroprotective effect of maltol on experimental glaucoma model

Other Titles
 녹내장 실험모델에 대한 말톨의 신경보호 효과 
Authors
 송유경 
Department
 Dept. of Ophthalmology (안과학교실) 
Issue Date
2015
Description
Dept. of Medicine/박사
Abstract
Purpose: Maltol (3-hydroxy-2-methyl-4-pyrone), formed through thermal degradation of starch, is found in caramelized foods, baked cereals, coffee, and Korean red ginseng. This study investigated the neuroprotective effects of maltol and its underlying mechanism in R28, rat embryonic precursor neuroretinal cells and retinal ganglion cells (RGCs) of optic nerve crush (ONC) mice.Methods: R28 cells were exposed to hydrogen peroxide (H2O2, 0.0 to 1.5 mM) with or without maltol (0.0 to 1.0 mM). Cell viability was monitored with the lactate dehydrogenase (LDH) assay and apoptosis was examined by the terminal deoxynucleotide transferase-mediated terminal uridine deoxynucleotidyl transferase nick end-labeling (TUNEL) method. ONC was performed unilaterally in adult male C57BL/6 mice without or with pre- or post-treatment of intraperitoneal (IP) maltol injection (100 mg/kg ) for 5 consecutive days. Each eye was enucleated after 1 day (n=15), 3 days (n=15), and 7 days (n=15). RGCs of ONC mice were assessed by H & E stain, immunohistochemistry and TUNEL method. To investigate the neuroprotective mechanism of maltol, phosphorylation of nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPK) were evaluated.Results: R28 cells exposed to H2O2 were found to have decreased viability in a dose- and time-dependent manner. However, H2O2-induced cytotoxicity was decreased with the addition of maltol. This H2O2-induced cytotoxicity caused apoptosis of R28 cells, characterized by DNA fragmentation. Apoptosis of oxidative stressed R28 cells with 1.0 mM H2O2was decreased with 1.0 mM maltol. Also, in RGCs of ONC mice, maltol not only increased cell viability but also attenuated DNA fragmentation. Western blot analysis of R28 cells and immunohistochemistry of ONC mice showed that maltol reduced phosphorylation of NF-κB and MAPKs.Conclusions: The present study
demonstrates that maltol inhibits apoptosis of R28 cells induced by H2O2 and RGCs induced by crush injury of optic nerve in mice. The mechanisms underlying this protection are not fully understood, but are associated with NF-kB and MAPK signaling pathways. This study provides evidence that maltol could be an innovative neuroprotective therapeutic agent for glaucoma.
Files in This Item:
T013441.pdf Download
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 3. Dissertation
Yonsei Authors
Song, Yoo Kyung(송유경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/145629
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