title: The neuroprotective effect of maltol against oxidative stress on rat retinal neuronal cells.
abstract: OBJECTIVE
  Maltol (3-hydroxy-2-methyl-4-pyrone), formed by the thermal degradation of starch, is found in coffee, caramelized foods, and Korean ginseng root. This study investigated whether maltol could rescue neuroretinal cells from oxidative injury in vitro.
  
  
  METHODS
  R28 cells, which are rat embryonic precursor neuroretinal cells, were exposed to hydrogen peroxide (H2O2, 0.0 to 1.5 mM) as an oxidative stress with or without maltol (0.0 to 1.0 mM). Cell viability was monitored with the lactate dehydrogenase assay and apoptosis was examined by the terminal deoxynucleotide transferase-mediated terminal uridine deoxynucleotidyl transferase nick end-labeling (TUNEL) method. To investigate the neuroprotective mechanism of maltol, the expression and phosphorylation of nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 were evaluated by Western immunoblot analysis.
  
  
  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. When R28 cells were exposed to 1.0 mM H2O2 for 24 hours, the cytotoxicity was 60.69 ± 5.71%. However, the cytotoxicity was reduced in the presence of 1.0 mM maltol. This H2O2-induced cytotoxicity caused apoptosis of R28 cells, characterized by DNA fragmentation. Apoptosis of oxidatively-stressed R28 cells with 1.0 mM H2O2 was decreased with 1.0 mM maltol, as determined by the TUNEL method. Western blot analysis showed that treatment with maltol reduced phosphorylation of NF-κB, ERK, and JNK, but not p38. The neuroprotective effects of maltol seemed to be related to attenuated expression of NF-κB, ERK, and JNK.
  
  
  CONCLUSIONS
  Maltol not only increased cell viability but also attenuated DNA fragmentation. The results obtained here show that maltol has neuroprotective effects against hypoxia-induced neuroretinal cell damage in R28 cells, and its effects may act through the NF-κB and mitogen-activated protein kinase signaling pathways.
authors: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors: Yookyung
authors: Y
authors: Song
authors: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors: Samin
authors: S
authors: Hong
authors: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors: Yoko
authors: Y
authors: Iizuka
authors: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors: Chan Yun
authors: CY
authors: Kim
authors: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors: Gong Je
authors: GJ
authors: Seong
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005421:Flavoring Agents / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D018384:Oxidative Stress / Q000187:drug effects*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D005421:Flavoring Agents; D011753:Pyrones; C008316:maltol
keywords: Maltol; Neuroprotection; Oxidative stress; Rat retinal neuronal cell
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