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.
Dawood, Amal F Maarouf, Amro Alzamil, Norah M Momenah, Maha A Shati, Ayed A Bayoumy, Nervana M Kamar, Samaa S Haidara, Mohamed A ShamsEldeen, Asmaa M Yassin, Hanaa Z
Dawood, Amal F
Maarouf, Amro
Alzamil, Norah M
Momenah, Maha A
Shati, Ayed A
Bayoumy, Nervana M
Kamar, Samaa S
Haidara, Mohamed A
ShamsEldeen, Asmaa M
Yassin, Hanaa Z
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.
MIDER Authors
Affiliations
Citations
Altmetric:
Date
2022-07-08
Type
Article
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