The effect of daidzein on renal injury in ovariectomized rats: interaction of angiotensin receptors and long non-coding RNAs H19, GAS5, MIAT, and Rian

Document Type : Full paper (Original article)


1 Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran

2 Cardiovascular Research Centre, Institute of Basic and Clinical Physiology Sciences, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran; Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman, Iran

3 Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran

4 Endocrinology and Metabolism Research Centre, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

5 Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran; Physiology Research Centre, Institute of Neuropharmacology, Afzalipour Medical Faculty, Kerman, Iran

6 Pathology and Stem Cell Research Center, Department of Pathology, Kerman University of Medical Sciences, Kerman, Iran


Background: Renin-angiotensin system (RAS) is prominently associated with renal pathophysiology in postmenopausal women. Long non-coding RNAs (lncRNAs) H19, GAS5, MIAT, and Rian have been linked to the pathogenesis of renal injury. Aims: This study aimed to evaluate the beneficial effects of daidzein on unilateral ureteral obstruction (UUO) induced-renal injury in ovariectomized (OVX) rats through interaction with angiotensin AT1, Mas receptors, and lncRNAs. Methods: 84 female rats were ovariectomized (OVX) two weeks before performing obstruction of the left kidney ureter (UUO). The animals were then randomly divided into four main groups (n=21): Sham+DMSO, UUO+DMSO, UUO+17β-Estradiol (E2) (positive control), and UUO+daidzein. Each main group comprised three subgroups (n=7) and were treated with saline, A779 (MasR antagonist), or losartan (AT1R antagonist) for 15 days. On day 16, the animals were euthanized, and the left kidneys were harvested for histopathology and lncRNAs expression assays. Results: UUO significantly increased kidney tissue damage score (KTDS) in the UUO rats, increased the expression of H19 and MIAT, and decreased the expression of GAS5 and Rian. Daidzein alone and in co-treatment with losartan or A779 reversed these effects. Daidzein with 1 mg/kg dose was more effective than E2. Conclusion: Daidzein alone and in co-treatment with A779 and losartan improved renal injury in UUO rats and recovered dysregulated expression of UUO-related lncRNAs through modulating MasR and AT1R receptors, associating with modulation of the expression of lncRNAs. Daidzein could be considered a renoprotective phytoestrogen substitute for E2 therapy in postmenopausal women suffering from renal diseases.


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