The novel compound Sul-121 preserves endothelial function and inhibits progression of kidney damage in type 2 Diabetes Mellitus in mice
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) w...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 September 2017
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| In: |
Scientific reports
Year: 2017, Volume: 7 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-11582-6 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/s41598-017-11582-6 Verlag, Volltext: https://www.nature.com/articles/s41598-017-11582-6 
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| Author Notes: | S.P.H. Lambooy, A. Bidadkosh, D. Nakladal, A. van Buiten, R.a.T. Girgis, A.C. van der Graaf, T.J. Wiedenmann, R.A. Koster, P. Vogelaar, H. Buikema, R.H. Henning, L.E. Deelman |
| Summary: | 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. |
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| Item Description: | Gesehen am 23.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-11582-6 |