Role of Oxidative Stress and Reduced Endogenous Hydrogen Sulfide in Diabetic Nephropathy

Drug Des Devel Ther. 2021 Mar 5:15:1031-1043. doi: 10.2147/DDDT.S291591. eCollection 2021.

Abstract

Purpose: Persistent hyperglycemia lead towards depletion of hydrogen sulfide (H2S) resulting in generation of oxidative stress and diabetic nephropathy. The aim of the current study was to explore the antioxidant potential of H2S and captopril, a -SH containing compound in streptozotocin (STZ)-induced diabetic nephropathy.

Methods: Fifty four Wistar-Kyoto (WKY) rats male (200-250g) were divided into nine groups (n=6) with each group injected once with STZ (60mg/kg i.p) except normal control. After 3 weeks of induction of diabetes, groups were assigned as normal control, diabetic control, diabetic-captopril, diabetic-NaHS, diabetic-captopril-NaHS, diabetic-spironolactone, diabetic-metformin, diabetic-metformin-NaHS and diabetic-vitamin-c. All the animals were served with normal saline (N/S 4mL/kg p.o), captopril (50mg/kg/day p.o), sodium hydrosulfide (NaHS) (56µmol/kg i.p), spironolactone (50mg/kg/day s.c), metformin (500mg/kg/day p.o) and vitamin-c (50mg/kg p.o) on daily basis for next 4 weeks, respectively. Metabolic studies, H2S levels, renal hemodynamics and oxidative stress markers were analyzed at 0, 14 and 28 days followed by histopathological analysis of renal tissues.

Results: The results showed decreased H2S levels, body weight, sodium to potassium ratio, glutathione (GSH), superoxide dismutase (SOD), total antioxidant assay (T-AOC) with malondialdehyde (MDA) and blood glucose levels significantly increased among diabetic rats. Treatment with captopril, NaHS, metformin, spironolactone and vitamin C showed significant improvement among renal hemodynamics and oxidative stress markers, respectively. But treatment groups like NaHS in combination with captopril and metformin showed more pronounced effects.

Conclusion: The observations suggest that H2S mediated protective effects on STZ-induced diabetic nephropathy may be associated with reduced oxidative stress via augmenting the antioxidant effect.

Keywords: captopril; diabetic nephropathy; oxidative stress; renal tissue; sodium hydrosulfide; streptozotocin.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Dose-Response Relationship, Drug
  • Hydrogen Sulfide / metabolism*
  • Male
  • Molecular Structure
  • Oxidative Stress
  • Protective Agents / metabolism*
  • Rats
  • Rats, Inbred WKY
  • Streptozocin / administration & dosage
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Protective Agents
  • Streptozocin
  • Hydrogen Sulfide