Nejvíce citovaný článek - PubMed ID 28400915
Molecular Hydrogen Effectively Heals Alkali-Injured Cornea via Suppression of Oxidative Stress
Corneal alkali burns are potentially blinding injuries. Alkali induces oxidative stress in corneas followed by excessive corneal inflammation, neovascularization, and untransparent scar formation. Molecular hydrogen (H2), a potent reactive oxygen species (ROS) scavenger, suppresses oxidative stress and enables corneal healing when applied on the corneal surface. The purpose of this study was to examine whether the H2 pretreatment of healthy corneas evokes a protective effect against corneal alkali-induced oxidative stress. Rabbit eyes were pretreated with a H2 solution or buffer solution, by drops onto the ocular surface, and the corneas were then burned with 0.25 M NaOH. The results obtained with immunohistochemistry and pachymetry showed that in the corneas of H2-pretreated eyes, slight oxidative stress appeared followed by an increased expression of antioxidant enzymes. When these corneas were postburned with alkali, the alkali-induced oxidative stress was suppressed. This was in contrast to postburned buffer-pretreated corneas, where the oxidative stress was strong. These corneas healed with scar formation and neovascularization, whereas corneas of H2-pretreated eyes healed with restoration of transparency in the majority of cases. Corneal neovascularization was strongly suppressed. Our results suggest that the corneal alkali-induced oxidative stress was reduced via the increased antioxidant capacity of corneal cells against reactive oxygen species (ROS). It is further suggested that the ability of H2 to induce the increase in antioxidant cell capacity is important for eye protection against various diseases or external influences associated with ROS production.
- MeSH
- alkálie toxicita MeSH
- antioxidancia metabolismus MeSH
- chemické popálení farmakoterapie metabolismus patologie MeSH
- epitelové buňky účinky léků metabolismus patologie MeSH
- hojení ran účinky léků MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- neovaskularizace rohovky prevence a kontrola MeSH
- oxidační stres účinky léků MeSH
- popálení oka chemicky indukované farmakoterapie metabolismus patologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rohovka krevní zásobení účinky léků metabolismus patologie MeSH
- vodík farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- odvolaná publikace MeSH
- Názvy látek
- alkálie MeSH
- antioxidancia MeSH
- reaktivní formy kyslíku MeSH
- vodík MeSH
Our previous research revealed that trehalose, a nonreducing disaccharide of glucose and an important stress responsive factor, proved to have anti-inflammatory, antiapoptotic, and particularly antioxidant properties in UVB-irradiated corneas. Trehalose reduced oxidative stress in corneas induced by UVB irradiation, by means of a decrease in the antioxidant/prooxidant imbalance in the corneal epithelium. In this study, we demonstrate that trehalose of 3% or 6% concentration in eye drops directly decreases oxidative stress in UVB-irradiated corneas, by removing the excessive amount of reactive oxygen species (ROS). Trehalose drops applied on corneas during UVB irradiation once daily for four days resulted in a reduction or even absence of the oxidative stress, DNA damage, and peroxynitrite formation (detected by nitrotyrosine residues), seen in buffer-treated corneas. Furthermore, trehalose treatment applied curatively after repeated irradiation for the subsequent fourteen days led to the renewal of corneal transparency and significant suppression or even absence of neovascularization. This was in contrast to buffer-treated irradiated corneas, where the intracorneal inflammation was developed and the untransparent corneas were vascularized. In conclusion, the treatment of UVB-irradiated corneas with trehalose eye drops removed the excessive amount of ROS in the corneal epithelium, leading to the suppression of oxidative stress and favorable corneal healing. The 6% trehalose showed a higher intensive antioxidant effect.
- MeSH
- hojení ran účinky léků účinky záření MeSH
- interleukin-1beta metabolismus MeSH
- keratiny metabolismus MeSH
- králíci MeSH
- oxidační stres * účinky léků účinky záření MeSH
- poranění rohovky farmakoterapie MeSH
- poškození DNA MeSH
- reaktivní formy kyslíku metabolismus MeSH
- reepitalizace účinky léků účinky záření MeSH
- rohovka účinky léků patologie účinky záření MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- trehalosa farmakologie terapeutické užití MeSH
- tyrosin analogy a deriváty metabolismus MeSH
- ultrafialové záření * MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- odvolaná publikace MeSH
- Názvy látek
- 3-nitrotyrosine MeSH Prohlížeč
- interleukin-1beta MeSH
- keratiny MeSH
- reaktivní formy kyslíku MeSH
- synthasa oxidu dusnatého, typ II MeSH
- trehalosa MeSH
- tyrosin MeSH
- vaskulární endoteliální růstový faktor A MeSH
The aim of this study is to examine whether molecular hydrogen (H2) is able to reduce oxidative stress after corneal damage induced by UVB irradiation. We previously found that UVB irradiation of the cornea caused the imbalance between the antioxidant and prooxidant enzymes in the corneal epithelium, followed by the imbalance between metalloproteinases and their physiological inhibitors (imbalances in favour of prooxidants and metalloproteinases) contributing to oxidative stress and development of the intracorneal inflammation. Here we investigate the effect of H2 dissolved in PBS in the concentration 0.5 ppm wt/vol, applied on rabbit corneas during UVB irradiation and healing (UVB doses 1.01 J/cm2 once daily for four days). Some irradiated corneas remained untreated or buffer treated. In these corneas the oxidative stress appeared, followed by the excessive inflammation. Malondiladehyde and peroxynitrite expressions were present. The corneas healed with scar formation and neovascularization. In contrast, in H2 treated irradiated corneas oxidative stress was suppressed and malondiladehyde and peroxynitrite expressions were absent. The corneas healed with the restoration of transparency. The study provides the first evidence of the role of H2 in prevention of oxidative and nitrosative stress in UVB irradiated corneas, which may represent a novel prophylactic approach to corneal photodamage.
- MeSH
- králíci MeSH
- kyselina peroxydusitá metabolismus MeSH
- malondialdehyd metabolismus MeSH
- oxidační stres účinky léků účinky záření MeSH
- poranění rohovky farmakoterapie metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rohovka účinky léků metabolismus účinky záření MeSH
- ultrafialové záření * MeSH
- vodík terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- odvolaná publikace MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kyselina peroxydusitá MeSH
- malondialdehyd MeSH
- reaktivní formy kyslíku MeSH
- vodík MeSH