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

异甘草素 医学 肾脏疾病 可溶性鸟苷酰环化酶 环磷酸鸟苷 内分泌学 内科学 药理学 高磷血症 一氧化氮 鸟苷酸环化酶
作者
Hebatallah Husseini Atteia,Eman Alamri,Nizar Sirag,Nahla Zidan,Raghad Humod Aljohani,Sharifa Alzahrani,Manar Hamed Arafa,Nanies Sameeh Mohammad,Mervat E. Asker,Sawsan A. Zaitone,Amr T. Sakr
出处
期刊:Life Sciences [Elsevier]
卷期号:317: 121460-121460 被引量:8
标识
DOI:10.1016/j.lfs.2023.121460
摘要

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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