Treatment with hydrogen sulfide alleviates streptozotocin-induced diabetic retinopathy in rats

Br J Pharmacol. 2013 Jun;169(3):619-31. doi: 10.1111/bph.12163.

Abstract

Background and purpose: Retinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)-induced diabetic retinopathy in rats.

Experimental approach: Rats were injected with a single i.p. injection of STZ (60 mg·kg⁻¹) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg⁻¹·d⁻¹ of 0.28 mol·L⁻¹ NaHS, a donor of H₂S) for 14 weeks.

Key results: Treatment with H₂S had no significant effect on blood glucose in STZ-induced diabetic rats. Treatment with exogenous H₂S enhanced H₂S levels in both plasma and retinas of STZ-induced diabetic rats. Treatment with H₂S in STZ-treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b-waves and oscillatory potentials and expression of synaptophysin and brain-derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down-regulated expressions of HIF-1α and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin β1 and collagen IVα3 expression in retinas of STZ-induced diabetic rats. Treatment with H₂S in retinas of STZ-induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF-κB activation and attenuated inflammation.

Conclusions and implications: Treatment with H₂S alleviates STZ-induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antioxidants / administration & dosage
  • Antioxidants / metabolism
  • Antioxidants / pharmacokinetics
  • Antioxidants / therapeutic use*
  • Capillary Permeability / drug effects
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / prevention & control*
  • Ependymoglial Cells / cytology
  • Ependymoglial Cells / drug effects*
  • Ependymoglial Cells / metabolism
  • Ependymoglial Cells / pathology
  • Gasotransmitters / administration & dosage
  • Gasotransmitters / metabolism
  • Gasotransmitters / pharmacokinetics
  • Gasotransmitters / therapeutic use
  • Hydrogen Sulfide / administration & dosage
  • Hydrogen Sulfide / metabolism
  • Hydrogen Sulfide / pharmacokinetics
  • Hydrogen Sulfide / therapeutic use*
  • Injections, Intraperitoneal
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Retina / cytology
  • Retina / drug effects
  • Retina / metabolism
  • Retina / pathology
  • Retinal Vessels / cytology
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology
  • Streptozocin
  • Sulfides / administration & dosage
  • Tissue Distribution

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Gasotransmitters
  • Sulfides
  • Streptozocin
  • sodium bisulfide
  • Hydrogen Sulfide