Role of Oxidative Stress and Reduced Endogenous Hydrogen Sulfide in Diabetic Nephropathy
Received 11 November 2020
Accepted for publication 15 February 2021
Published 5 March 2021 Volume 2021:15 Pages 1031—1043
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Anastasios Lymperopoulos
Arslan Hussain Lodhi,1 Fiaz-ud-Din Ahmad,1 Kainat Furwa,1 Asadullah Madni2
1Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
Correspondence: Fiaz-ud-Din Ahmad
Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Khawaja Fareed Campus, Railway Road, Bahawalpur, 63100, Pakistan
Email [email protected]
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, streptozotocin, sodium hydrosulfide
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