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The Novel Compound Sul-121 Preserves Endothelial Function and Inhibits Progression of Kidney Damage in Type 2 Diabetes Mellitus in Mice

Lambooy, S. P. H., Bidadkosh, A., Nakladal, D., van Buiten, A., Girgis, R. A. T., van der Graaf, A. C., Wiedenmann, T. J., Koster, R. A., Vogelaar, P., Buikema, H., Henning, R. H. & Deelman, L. E. 11-Sep-2017 In : Scientific Reports. 7, 1, 13 p., 11165

Research output: Scientific - peer-reviewArticle

Diabetic nephropathy is still a common complication of type 2 diabetes mellitus (T2DM) and improvement of endothelial dysfunction (ED) and inhibition of reactive oxygen species (ROS) are considered important targets for new therapies. Recently, we developed a new class of compounds (Sul compounds) which inhibit mitochondrial ROS production. Here, we tested the therapeutic effects of Sul-121 on ED and kidney damage in experimental T2DM. Diabetic db/db and lean mice were implanted with osmotic pumps delivering Sul-121 (2.2 mg/kg/day) or vehicle from age 10 to 18 weeks. Albuminuria, blood pressure, endothelial mediated relaxation, renal histology, plasma creatinine, and H2O2 levels were assessed. Sul-121 prevented progression of albuminuria and attenuated kidney damage in db/db, as evidenced by lower glomerular fibronectin expression (~50%), decreased focal glomerular sclerosis score (~40%) and normalization of glomerular size and kidney weight. Further, Sul-121 restored endothelium mediated vasorelaxation through increased production of Nitric Oxide production and normalized plasma H2O2 levels. Sul-121 treatment in lean mice demonstrated no observable major side-effects, indicating that Sul-121 is well tolerated. Our data show that Sul-121 inhibits progression of diabetic kidney damage via a mechanism that involves restoration of endothelial function and attenuation of oxidative stress.

Original languageEnglish
Article number11165
Number of pages13
JournalScientific Reports
Volume7
Issue number1
StatePublished - 11-Sep-2017

    Keywords

  • HYPERPOLARIZING FACTOR, NATRIURETIC PEPTIDE, NEPHROPATHY, SUSCEPTIBILITY, PODOCYTES, DISEASE, HUMANS, MOUSE, CELLS, RAT

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