• Beneficial effect of daidzein on renal dysfunction, apoptosis and fibrosis in the ovariectomized rat: Role of angiotensin receptors and microRNAs
  • Majid Askaripour,1,* Hamid Najafipour,2 Shadan Saberi ,3 Fariba Poosti,4 Saleh Yazdani ,5 Soodeh Rajabi,6
    1. Department of Physiology, School of Medicine, Bam University of Medical Sciences, Bam, Iran.
    2. Department of Physiology and Pharmacology, and Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
    3. Department of Physiology and Pharmacology, Afzalipour Medical Faculty and Physiology Research Centre, Kerman University of Medical Sciences, Kerman, Iran
    4. Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
    5. VIB-KU Leuven Center for Microbiology, Leuven, Belgium
    6. Department of Physiology and Pharmacology, and Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran


  • Introduction: Chronic kidney disease (CKD), accompanied by renal dysfunction, fibrosis, and apoptosis, is highly prevalent in postmenopausal women. Here, we tested the hypothesis that the isoflavone daidzein may ameliorate renal dysfunction, apoptosis and fibrosis through angiotensin II type 1 (AT1R) and angiotensin 1-7 (MasR) receptors in association with microRNAs 33a and 27a.
  • Methods: Two weeks before the initiation of the experiments, rats (n=84) underwent ovariectomy (OVX). Then, unilateral ureteral obstruction (UUO) was performed in OVX rats, and animals were allocated to the following groups (n=21): sham vehicle (dimethyl sulfoxide; DMSO), UUO vehicle, UUO+17β-estradiol (E2), and UUO+daidzein. Each group encompassed three subgroups (n=7) treated with saline, A779 (MasR antagonist) or losartan (AT1R antagonist) for 15 days. The fractional urine excretion of sodium (FENa+) and potassium (FEK+), renal failure index (RFI), renal interstitial fibrosis (RIF index), glomerulosclerosis, renal miR-33a and miR-27a expressions and their target genes were analyzed. Apoptosis was measured by performing cleaved caspase-3 immunohistochemistry.
  • Results: UUO increased kidney weight, FENa+, FEK+, urine calcium, RFI, RIF index, glomerulosclerosis, and cleaved caspase-3. Moreover, expression of renal miR-33a and miR-27a, collagen3A1 and fibronectin mRNA and protein were upregulated post-UUO. Daidzein and E2 treatment with or without losartan or A779 alleviated renal dysfunction, apoptosis and fibrosis
  • Conclusion: Compared to E2, daidzein efficiently ameliorated renal dysfunction, apoptosis and interstitial fibrosis through modulation of miR-33a and miR-27a expression and their crosstalk with AT1R and MasR. Therefore, daidzein might be a promising candidate for treating CKD in postmenopausal and older women.
  • Keywords: Daidzein, ovariectomy, apoptosis, renal fibrosis, angiotensin receptor, microRNAs