The Novel Compound Sul-121 Preserves Endothelial Function and Inhibits Progression of Kidney Damage in Type 2 Diabetes Mellitus in Mice
| Autor: | T J Wiedenmann, Arash Bidadkosh, S. P. H. Lambooy, Leo E. Deelman, P. Vogelaar, R A T Girgis, Hendrik Buikema, A van Buiten, Robert H. Henning, Remco A. Koster, D. Nakladal, A C van der Graaf |
|---|---|
| Přispěvatelé: | Vascular Ageing Programme (VAP), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Medicine 030204 cardiovascular system & hematology SUSCEPTIBILITY Kidney Kidney Function Tests MOUSE Antioxidants Piperazines DISEASE Diabetic nephropathy Mice 0302 clinical medicine Medicine Diabetic Nephropathies Endothelial dysfunction lcsh:Science HYPERPOLARIZING FACTOR Multidisciplinary Histocytochemistry HUMANS Treatment Outcome medicine.anatomical_structure medicine.symptom medicine.medical_specialty Endothelium NEPHROPATHY Renal function Article Diabetes Mellitus Experimental Nephropathy 03 medical and health sciences Diabetes mellitus Internal medicine Albuminuria Animals Chromans business.industry NATRIURETIC PEPTIDE lcsh:R Hydrogen Peroxide medicine.disease 030104 developmental biology Endocrinology CELLS RAT lcsh:Q PODOCYTES business |
| Zdroj: | Scientific Reports Scientific Reports, 7(1):11165. Nature Publishing Group Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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