Abstract
Introduction:
The mechanism of beneficial effects of H2S in chronic kidney disease (CKD) is the aim of the present study to examine the effects of the H2S donor sodium hydrosulfide (NaHS) on renal function parameters, oxidative stress indices and expression levels of HIF-2α gene and erythropoietin protein in 5/6 nephrectomy-induced chronic renal failure in rats.
Methods and Materials:
Male rats were assigned into 3 groups (n = 8): Sham, CKD and NaHS groups. In the CKD group, 5/6 nephrectomy was performed. In the sham group, rats were anesthetized but 5/6 nephrectomy was not induced. In the NaHS group, 30 µmol/L of NaHS in drinking water for 8 weeks was adminstrated 4 weeks after 5/6 nephrectomy induction. At the end of the 12 week, blood and renal tissues were taken to evaluate renal function parameters, oxidative stress indices and expression levels of HIF-2α gene and erythropoietin protein.
Results
The induction of 5/6 nephrectomy significantly caused renal dysfunction, oxidative stress, increased HIF-2α gene expression and decreased erythropoietin levels in renal tissue samples. NaHS administration resulted in a marked improvement in renal function and oxidative stress indicators, a marked reduction in HIF-2α gene expression as well as an increase in erythropoietin protein levels in comparison with the CKD group.
Conclusion
In this study, regional hypoxia and oxidative stress in CKD, may cause the activation of toll-like receptors and stabilization of the HIFs complexes and due to destructive effects of CKD on the kidney tissues, erythropoietin synthesis was not increased. Administration of NaHS caused inhibition of toll-like receptors and increase the blood flow (vasodilation) on kidney tissue and up-regulating HIF-erythropoietin signalling pathway.