Abstract: SA-PO527
Semicarbazide-Sensitive Amine Oxidase (SSAO) Inhibition Ameliorates Albuminuria and Glomerulosclerosis but Does Not Significantly Improve Tubulointerstitial Fibrosis in Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Wong, May Yw, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
- Wong, Muh Geot, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
- Zaky, Amgad, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
- Gill, Anthony J., University of Sydney, St Leonards, New South Wales, Australia
- Pollock, Carol A., University of Sydney, St Leonards, New South Wales, Australia
- Saad, Sonia, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
Background
SSAO is an enzyme known for its dual function in mediating inflammation and reactive oxygen species production. However, the role of SSAO inhibitors in chronic kidney disease is unclear. We aimed to determine the effectiveness of a SSAO inhibitor (PXS4728A) as an antifibrotic agent using a diabetic model of chronic kidney fibrosis.
Methods
A streptozotocin-induced diabetic model in male eNOS-/-mice on a C57BL/6 background. Diabetic mice were treated with SSAOi for 24 weeks and outcomes compared with untreated diabetic mice and telmisartan treated animals as a comparator of current standard of care.
Results
Albuminuria, the extracellular matrix marker fibronectin, inflammatory marker expression of CD45 and oxidative stress, assessed by nitrotyrosine staining, were lower in diabetic mice treated with SSAOi compared with untreated diabetic mice. Glomerulosclerosis was reduced to a greater extent by SSAOi compared to telmisartan.
Conclusion
The effect of SSAO inhibition in diabetic mice resulted in a significant reduction in inflammation, oxidative stress, glomerulosclerosis and associated albuminuria compared to untreated diabetic mice. However, the effect of SSAOi was less obvious in the tubulointerstitial compartment than in the glomeruli. Therefore, SSAOi may be a potential target for diabetic glomerulosclerosis.
Parameters of studied animals
| n=6-8 | Control | Control + SSAOi | DM | DM+ SSAOi | DM + Telmi | DM+ Telmi+ SSAOi |
| Fasting Blood glucose level (mmol/L) | 9.5±0.44 | 10.2±0.41 | 20.0±0.60* | 20.7±0.77* | 24.2±1.06* | 20.2±1.0* |
| HbA1c (%) | 4.3±0.05 | 7.0±0.26* | 7.1±0.49* | 7.7±0.40* | 7.9±0.44* | |
| Weekly Insulin requirement (IU) | 0.1±0.05 | 0.04±0.02 | 0.3±0.09 | 0.1±0.04 | ||
| Urinary Albumin: Creatinine (ug/mg) | 113±17 | 104±13 | 597±163* | 401±123# | 187±42# | 345±74 |
SSAO inhibiton reduced glomerulosclerosis but not degree of tubulointerstitial fibrosis