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

Purpose: Persistent hyperglycemia lead towards depletion of hydrogen sulfide (H ₂ S) resulting in generation of oxidative stress and diabetic nephropathy. The aim of the current study was to explore the antioxidant potential of H ₂ S 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, H ₂ S 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 H ₂ S 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 H ₂ S mediated protective effects on STZ-induced diabetic nephropathy may be associated with reduced oxidative stress via augmenting the antioxidant effect.
Competing Interests: The authors declare no conflict of interest.
(© 2021 Hussain Lodhi et al.)