title: Sirtuin Type 1 Mediates the Retinal Protective Effect of Hydrogen-Rich Saline Against Light-Induced Damage in Rats.
abstract: OBJECTIVE
  Molecular hydrogen has been used as an antioxidant to treat many diseases in clinical and animal studies. However, the therapeutic mechanism of molecular hydrogen remains unclear. We previously reported mitigation of light-induced damage in the rat retina by intraperitoneal injection of hydrogen-rich saline (HRS). In the present study, we investigated whether Sirtuin Type 1 (Sirt1), a class III histone deacetylase, mediates the retinal protective effect of HRS in rats with light-induced retinal damage.
  
  
  METHODS
  Rats were treated with HRS for 5 days after intense light exposure, and then ERGs were performed and retinas were collected to evaluate the effect of HRS on Sirt1 expression. The necessity of Sirt1 for the retinal protective effect of HRS was investigated using the Sirt1 activator resveratrol, the Sirt1 inhibitor EX-527, and short interfering RNAs.
  
  
  RESULTS
  In light-damaged retinas, 5 days of HRS treatment increased Sirt1 expression, mitigated a- and b-wave amplitude reduction, and decreased the reduction of outer nuclear cell layers. The Sirt1 activator resveratrol mimicked the effect of HRS in light-damaged retinas. This result supported our hypothesis that Sirt1 mediates the protective effect of HRS. Additionally, the retinal protective effect of HRS was inhibited by both the Sirt1 inhibitor EX-527 and Sirt1 targeted short interfering RNAs. Hydrogen-rich saline also increased B-cell lymphoma 2 (Bcl-2) expression and the activity of the antioxidant enzyme superoxide dismutase (SOD). Conversely, HRS decreased Bcl2-associated X protein expression, cleaved caspase-3, and oxidant-stress product malondialdehyde (MDA) in a Sirt1-dependent manner.
  
  
  CONCLUSIONS
  Sirt1 mediates light-induced damage mitigation by HRS through inhibition of apoptosis and oxidant-stress.
authors.affiliation: Department of Clinical Aerospace Medicine Fourth Military Medical University, Xi'an, China.
authors.forename: Lin-Song
authors.initials: LS
authors.lastname: Qi
authors.affiliation: Department of Clinical Aerospace Medicine Fourth Military Medical University, Xi'an, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yao
authors.affiliation: Medical Experiment Center, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Ecomic Zone, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wei-Xun
authors.initials: WX
authors.lastname: Duan
authors.affiliation: Department of Clinical Aerospace Medicine Fourth Military Medical University, Xi'an, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Clinical Aerospace Medicine Fourth Military Medical University, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Aerospace Medicine Fourth Military Medical University, Xi'an, China.
authors.forename: Zuo-Ming
authors.initials: ZM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006859:Hydrogen / Q000494:pharmacology*; D008027:Light / Q000009:adverse effects; D008297:Male; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012164:Retinal Diseases / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics*; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D012965:Sodium Chloride; D012313:RNA; D006859:Hydrogen; D056564:Sirtuin 1