Daidzein Mitigates Oxidative Stress and Inflammation in the Injured Kidney of Ovariectomized Rats: AT1 and Mas Receptor Functions

Chronic kidney disease (CKD) is a health problem in postmenopausal women, and renal fibrosis is a common feature of CKD. In the renin-angiotensin system, oxidative stress and inflammation are involved in the pathogenesis of renal fibrosis. This study investigated the effect of the phytoestrogen daidzein on oxidative stress and inflammation and the mediation of the angiotensin AT1 and Mas receptors in a fibrotic model of kidney disease of ovariectomized (OVX) rats.

Unilateral ureteral obstruction (UUO) was performed to induce chronic renal inflammation and fibrosis in 84 OVX rats, which were divided into four main groups (each = 21) including sham + Vehicle (Veh.), UUO + Veh, UUO + estradiol (E2), and UUO + daidzein. Each main group composed of three subgroups (n = 7), which received saline, losartan (AT1R antagonist), or A779 (Mas receptor [MasR] antagonist) for 15 days after UUO or sham operation. Renal pathology, serum and kidney oxidants and antioxidants, malondialdehyde (MDA), nitric oxide metabolites (NOx), protein carbonyl (PC), and pro-inflammatory and anti- inflammatory cytokines were examined.

UUO increased renal glomerulosclerosis, inflammation, serum and kidney tissue MDA, NOx, and PC together with an increase in TNF-α, IL-1β, and IL-6 expression. Moreover, UUO decreased superoxide dismutase and glutathione peroxidase and catalase activity, total antioxidant capacity, and IL-10 level in the serum and kidney tissue. AT1R blockade reduced and MasR blockade worsened renal impairment. Daidzein and E2 alone and in co-treatment with losartan significantly ameliorated these effects.

Via interaction with AT1R and MasRs, daidzein improved glomerulosclerosis, oxidative stress, and inflammation in UUO-OVX rats. Daidzein may be a candidate for estrogen replacement therapy in postmenopausal or older women against postmenopausal kidney damage.