Metformin Is associated with the inhibition of renal artery AT1R/ET-1/iNOS Axis in a rat model of diabetic nephropathy with suppression of inflammation and oxidative stress and kidney injury.
Abstract
Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A significant correlation between the AT1R/ET-1/iNOS axis, inflammation, fibrosis and glycemia was observed. Thus, diabetes is associated with the augmentation of the renal artery AT1R/ET-1/iNOS axis as well as renal injury and hypertension while being protected by metformin.
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Date
2022-07-08
Type
Article
Subject
Human physiology, Biochemistry, Paediatrics, Cardiology
Collections
Citation
Dawood AF, Maarouf A, Alzamil NM, Momenah MA, Shati AA, Bayoumy NM, Kamar SS, Haidara MA, ShamsEldeen AM, Yassin HZ, Hewett PW, Al-Ani B. Metformin Is Associated with the Inhibition of Renal Artery AT1R/ET-1/iNOS Axis in a Rat Model of Diabetic Nephropathy with Suppression of Inflammation and Oxidative Stress and Kidney Injury. Biomedicines. 2022 Jul 8;10(7):1644. doi: 10.3390/biomedicines10071644
Journal / Source Title
Biomedicines
DOI
10.3390/biomedicines10071644
PMID
35884947
Publisher
MDPI
Publisher’s URL
http://www.mdpi.com/journal/biomedicines
https://www.ncbi.nlm.nih.gov/pmc/journals/3168/
https://www.ncbi.nlm.nih.gov/pmc/journals/3168/