Soluble guanylate cyclase agonist, isoliquiritigenin attenuates renal damage and aortic calcification in a rat model of chronic kidney failure

Soluble guanylate cyclase agonist, isoliquiritigenin attenuates renal damage and aortic calcification in a rat model of chronic kidney failure

Chronic kidney disease (CKD) is a growing fatal health problem worldwide associated with vascular calcification. Therapeutic approaches are limited with higher costs and poor outcomes. Adenine supplementation is one of the most relevant CKD models to human. Insufficient Nitric Oxide (NO)/ cyclic Gua...

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Published in:Life sciences (1973) Vol. 317; p. 121460
Main Authors: Atteia, Hebatallah Husseini, Alamri, Eman Saad, Sirag, Nizar, Zidan, Nahla Salah, Aljohani, Raghad Humod, Alzahrani, Sharifa, Arafa, Manar Hamed, Mohammad, Nanies Sameeh, Asker, Mervat Elsayed, Zaitone, Sawsan A., Sakr, Amr Tawfik
Format: Journal Article
Language:English
Published: Netherlands Elsevier Inc 15-03-2023
Subjects:
Adenine
Animals
cGMP
Chalcones
Cyclic GMP - metabolism
Fibrosis
Guanylate Cyclase
Humans
Isoliquiritigenin
Kidney Failure, Chronic
Male
Nitric Oxide - metabolism
Rats
Rats, Wistar
Renal fibrosis
Renal Insufficiency, Chronic
Soluble Guanylyl Cyclase
Vascular calcification
α-SMA
Adenine
Vascular calcification
Isoliquiritigenin
α-SMA
cGMP
Renal fibrosis
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Summary:Chronic kidney disease (CKD) is a growing fatal health problem worldwide associated with vascular calcification. Therapeutic approaches are limited with higher costs and poor outcomes. Adenine supplementation is one of the most relevant CKD models to human. Insufficient Nitric Oxide (NO)/ cyclic Guanosine Monophosphate (cGMP) signaling plays a key role in rapid development of renal fibrosis. Natural products display proven protection against CKD. Current study therefore explored isoliquiritigenin, a bioflavonoid extracted from licorice roots, potential as a natural activator for soluble Guanylate Cyclase (sGC) in a CKD rat model. 60 male Wistar rats were grouped into Control group (n = 10) and the remaining rats received adenine (200 mg/kg, p.o) for 2 wk to induce CKD. They were equally sub-grouped into: Adenine untreated group and 4 groups orally treated by isoliquiritigenin low or high dose (20 or 40 mg/kg) with/without a selective sGC inhibitor, ODQ (1-H(1,2,4)oxadiazolo(4,3-a)-quinoxalin-1-one, 2 mg/kg, i.p) for 8 wk. Long-term treatment with isoliquiritigenin dose-dependently and effectively amended adenine-induced chronic renal and endothelial dysfunction. It not only alleviated renal fibrosis and apoptosis markers but also aortic calcification. Additionally, this chalcone neutralized renal inflammatory response and oxidative stress. Isoliquiritigenin beneficial effects were associated with up-regulation of serum NO, renal and aortic sGC, cGMP and its dependent protein kinase (PKG). However, co-treatment with ODQ antagonized isoliquiritigenin therapeutic impact. Isoliquiritigenin seems to exert protective effects against CKD and vascular calcification by activating sGC, increasing cGMP and its downstream PKG.
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ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2023.121460