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Hydrogen sulfide modulates SIRT1 and suppresses oxidative stress in diabetic nephropathy

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Abstract

DN is recognized as not only a leading cause of end stage renal disease (ESRD) but also an independent risk factor for cardiovascular disease (CVD). Novel therapeutic approaches to diabetic nephropathy (DN) are needed, or else, healthcare resources will be overwhelmed by the expected worldwide increase in associated cases of ESRD and CVD. Reactive oxygen species (ROS) and advanced glycation end product (AGE) are implicated in the development of DN. Hydrogen sulfide (H2S) is known for its antioxidant and antiapoptotic characteristics. Simultaneously diabetics have lower H2S levels. Thus, it is worth investigating the use of H2S in treatment of DN. To investigate the potential therapeutic role of H2S in DN. Sixty male rats were divided into four groups: control, DN, DN+NaHS30 µmol/kg/day and DN+NaHS100 µmol/kg/day. Fasting blood sugar (FBS), kidney function tests, SIRT1 activity, superoxide dismutase activity (SOD), malondialdehyde (MDA) and expression of caspase3 and p53 in renal tissues were assessed. Kidney was examined histopathologically. DN rats had higher FBS, renal dysfunction, decreased SIRT1 and SOD activity levels, increased caspase3 and p53 relative expression and increased MDA in renal tissues. NaHS increased SIRT1 and reversed biochemical, apoptotic, oxidant and pathologic parameters characteristic of DN, with better results using a dose of 100 µmol/kg/day. H2S has a protective role against DN through decreasing FBS, ROS, apoptosis and upregulating SIRT1, thus preserving renal cells from further damage caused by DM.

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Acknowledgements

We feel grateful for the staff members of molecular biology units of Biochemistry department, faculty of medicine, Cairo University.

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This work was supported by Cairo University, Cairo, Egypt.

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Authors and Affiliations

  1. Medical Biochemistry and Molecular Biology Department, Kasr Al Ainy School of Medicine, Cairo University, Kasr Al Ainy St., El Manial, 11562, Cairo, Egypt

    Hanan H. Ahmed, Fatma M. Taha, Heba S. Omar & Heba M. Elwi

  2. Pathology Department, Kasr Al Ainy School of Medicine, Cairo University, Kasr Al Ainy St., El Manial, 11562, Cairo, Egypt

    Marwa Abdelnasser

  3. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Kasr Alainy St., El Manial, 11562, Cairo, Egypt

    Heba S. Omar

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  1. Hanan H. Ahmed
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Ahmed, H.H., Taha, F.M., Omar, H.S. et al. Hydrogen sulfide modulates SIRT1 and suppresses oxidative stress in diabetic nephropathy. Mol Cell Biochem 457, 1–9 (2019). https://doi.org/10.1007/s11010-019-03506-x

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