Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats

Curr Eye Res. 2013 Mar;38(3):396-404. doi: 10.3109/02713683.2012.748919. Epub 2012 Dec 19.


Purpose: Diabetic retinopathy (DR) is characterized by increased oxidative and nitrosative stress, both of which lead to neurotoxicity and vascular permeability. Previous studies on a variety of organs indicate that hydrogen-rich saline not only has considerable antioxidant and anti-inflammatory properties, but also suppresses oxidative stress-induced injury. In the present study, we assessed the effects of hydrogen-rich saline on neurovascular dysfunction and oxidative stress in an animal model (rat) of DR.

Materials and methods: Male Sprague-Dawley rats with streptozotocin (STZ)-induced diabetes mellitus (DM) were injected intraperitoneally with 5 ml/kg hydrogen-saturated (experimental) or plain (control) saline daily for one month. Visual function and blood-retinal barrier (BRB) integrity were evaluated by electroretinography (ERG) and bovine serum albumin (BSA)-fluorescence, respectively. Histological changes in the inner retina were assessed by light microscopy. Biomarkers of oxidative stress, including 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OH-dG), and antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione transferase, were evaluated by ELISA. Synaptophysin and brain-derived neurotrophic factor (BDNF) levels were measured by immunoblotting.

Results: STZ-diabetic rats were marked by clearly reduced b-wave amplitudes and oscillatory potentials, DM-related BRB breakdown and histological changes in the inner retina, all of which were suppressed following treatment with hydrogen-rich saline. Furthermore, hydrogen-rich saline reduced oxidative stress, increased antioxidant enzyme activities and preserved synaptophysin and BDNF levels in the diabetic rat retina.

Conclusions: Based on its inhibition of oxidative stress and up-regulation of anti-oxidative enzymes, we conclude that hydrogen-rich saline is a potentially valuable therapeutic modality for the treatment of DR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aldehydes / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Blood-Retinal Barrier / drug effects
  • Blotting, Western
  • Body Weight
  • Brain-Derived Neurotrophic Factor / metabolism
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / physiopathology
  • Diabetic Retinopathy / prevention & control*
  • Electroretinography
  • Enzyme-Linked Immunosorbent Assay
  • Male
  • Oxidative Stress / drug effects*
  • Oxidoreductases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Neovascularization / physiopathology
  • Retinal Neovascularization / prevention & control*
  • Sodium Chloride / pharmacology*
  • Synaptophysin / metabolism


  • Aldehydes
  • Blood Glucose
  • Brain-Derived Neurotrophic Factor
  • Synaptophysin
  • Sodium Chloride
  • 8-Hydroxy-2'-Deoxyguanosine
  • Oxidoreductases
  • Deoxyguanosine
  • 4-hydroxy-2-nonenal