H2S donors attenuate diabetic nephropathy in rats: Modulation of oxidant status and polyol pathway

Pharmacol Rep. 2015 Feb;67(1):17-23. doi: 10.1016/j.pharep.2014.08.001. Epub 2014 Aug 20.

Abstract

Background: Sulfurous mineral water and its main active ingredient sodium hydrosulfide (NaHS) are major sources of H2S. The present study aimed to explore their protective effect on one of the serious long-term complications of diabetes; diabetic nephropathy.

Methods: Sulfurous mineral water (as drinking water), NaHS (14 μmol/kg/day; ip), and gliclazide (10mg/kg; po) were administered daily for 6 weeks to streptozotocin (STZ)-diabetic rats.

Results: STZ-induced diabetes was associated with body weight reduction, hyperglycemia, overproduction of glycated hemoglobin, as well as decline in serum insulin, C-peptide, and insulin like growth factor-I. Besides, diabetes impaired kidney functions and imposed oxidative and nitrosative stress as manifested by elevated contents of renal thiobarbituric acid reactive substances and nitric oxide, parallel to reduced glutathione content. These deleterious effects were antagonized by sulfurous water and to a better extent by NaHS. Activities of myeloperoxidase and sorbitol dehydrogenase were not altered by STZ or any of the treatments. However, STZ-induced diabetes was accompanied by an increment of aldose reductase which was only mitigated by gliclazide and NaHS. Histopathological examination of kidney sections corroborated the biochemical findings.

Conclusion: This study suggests a novel therapeutic approach for diabetic nephropathy using H2S donors.

Keywords: Diabetic nephropathy; H(2)S; Insulin like growth factor-I (IGF-I); Polyol pathway; Sulfurous mineral water.

MeSH terms

  • Aldehyde Reductase / metabolism
  • Animals
  • Antioxidants / metabolism*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetic Nephropathies / drug therapy*
  • Gliclazide / therapeutic use
  • Hydrogen Sulfide / metabolism*
  • Hypoglycemic Agents / therapeutic use
  • Insulin-Like Growth Factor I / metabolism
  • Kidney Function Tests
  • L-Iditol 2-Dehydrogenase / metabolism
  • Male
  • Mineral Waters
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Antioxidants
  • Hypoglycemic Agents
  • Mineral Waters
  • Thiobarbituric Acid Reactive Substances
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I
  • L-Iditol 2-Dehydrogenase
  • Aldehyde Reductase
  • Peroxidase
  • Gliclazide
  • Hydrogen Sulfide