Exercise training improves diabetic renal injury by reducing fetuin-A, oxidative stress and inflammation in type 2 diabetic rats.

Background: Diabetic kidney disease (DKD) stands as a primary contributor to end-stage renal disease, associated with heightened mortality in cardiovascular diseases. This study aimed to explore the impact of an eight-week high-intensity interval training (HIIT) on renal injury in diabetic rats. Methods: Twenty-eight male Wistar rats were randomly allocated into four groups: healthy control (CTL), diabetic control (DC), exercise (EX), and diabetes-exercise (D + EX). Induction of diabetes in the DC and D + EX groups occurred through a two-month high-fat diet followed by a single dose of 35 mg/kg streptozotocin (STZ). Rats in the EX and D + EX groups underwent 4-10 intervals of HIIT (80-100% Vmax) over 8 weeks. Subsequently, pathological and biochemical parameters were assessed in the serum and kidney tissue of the experimental groups. Results: In the DC group, diabetes led to elevated kidney damage, glomerulosclerosis, fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index, animal weight, kidney dysfunction, albuminuria, and glomerular filtration rate. Additionally, serum and kidney levels of fetuin-A increased, along with kidney levels of KIM-1. Mechanistically, diabetes induction resulted in kidney inflammation by elevating levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-ß), and interleukin 6 (IL-6), while reducing IL-10 levels and increasing the IL-6/IL-10 ratio. Furthermore, diabetes triggered renal oxidative stress, evidenced by increased Malondialdehyde (MDA) levels and decreased levels of glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD). HIIT mitigated the adverse effects of diabetes in the D + EX group compared to the DC group. Conclusion: Our findings suggest that HIIT ameliorates type 2 diabetes (T2D)-induced kidney damage by mitigating inflammation, lowering serum levels of fetuin-A, and bolstering antioxidant defenses. This study highlights the potential of HIIT as a time-efficient intervention for diabetic nephropathy.

Interaction of estradiol and renin-angiotensin system with microRNAs-21 and -29 in renal fibrosis: focus on TGF-ß/smad signaling pathway.

Kidney fibrosis is one of the complications of chronic kidney disease (CKD (and contributes to end-stage renal disease which requires dialysis and kidney transplantation. Several signaling pathways such as renin-angiotensin system (RAS), microRNAs (miRNAs) and transforming growth factor-ß1 (TGF-ß1)/Smad have a prominent role in pathophysiology and progression of renal fibrosis. Activation of classical RAS, the elevation of angiotensin II (Ang II) production and overexpression of AT1R, develop renal fibrosis via TGF-ß/Smad pathway. While the non-classical RAS arm, Ang 1-7/AT2R, MasR reveals an anti-fibrotic effect via antagonizing Ang II. This review focused on studies illustrating the interaction of RAS with sexual female hormone estradiol and miRNAs in the progression of renal fibrosis with more emphasis on the TGF-ß signaling pathway. MiRNAs, especially miRNA-21 and miRNA-29 showed regulatory effects in renal fibrosis. Also, 17ß-estradiol (E2) is a renoprotective hormone that improved renal fibrosis. Beneficial effects of ACE inhibitors and ARBs are reported in the prevention of renal fibrosis in patients. Future studies are also merited to delineate the new therapy strategies such as miRNAs targeting, combination therapy of E2 or HRT, ACEis, and ARBs with miRNAs mimics and antagomirs in CKD to provide a new therapeutic approach for kidney patients.

Isoflavone daidzein ameliorates renal dysfunction and fibrosis in a postmenopausal rat model: Intermediation of angiotensin AT1 and Mas receptors and microRNAs 33a and 27a.

Objectives: Chronic kidney disease (CKD), accompanied by renal dysfunction, fibrosis, and apoptosis, is highly prevalent in postmenopausal women. We tested the hypothesis that isoflavone daidzein may ameliorate renal dysfunction and fibrosis through angiotensin II type 1 (AT1R) and angiotensin 1-7 (MasR) receptors in association with microRNAs 33a and 27a. Materials and 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 1%), UUO vehicle, UUO+17ß-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, miR-33a, and miR-27a expressions and their target genes were analyzed. Apoptosis was measured via 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 mRNA, and protein were up-regulated post-UUO. Daidzein treatment alleviated the harmful effects of UUO especially in co-treatment with losartan. They also masked the anticipated worsening effects of A779 on UUO. Conclusion: Compared with E2, daidzein efficiently ameliorated renal dysfunction, fibrosis, and apoptosis 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.

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

INTRODUCTION: 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. METHODS: 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 antiinflammatory cytokines were examined. RESULTS: UUO increased renal glomerulosclerosis, inflammation, serum and kidney tissue MDA, NOx, and PC together with an increase in TNF-α, IL-1ß, 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. CONCLUSION: 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.  DOI: 10.52547/ijkd.6602.

Epidemiological update on prevalence and incidence of overweight and obesity in adults in the south-east of the Islamic Republic of Iran: findings from the Kerman Coronary Artery Diseases Risk Factors Study (KERCADRS).

BACKGROUND: Obesity is common worldwide, especially in low- and middle-income countries. AIMS: To update data on the prevalence of overweight, obesity and central obesity, and to measure incidence rates for such outcomes in adults living in the south-east of the Islamic Republic of Iran. METHODS: We enrolled 9997 adults (aged 15-80 years) between 2014 and 2018 (phase 2); 2820 of whom had participated in phase 1 (2009-2011). Participants were examined for overweight, obesity, central obesity, diabetes, hypertension, low physical activity, and dyslipidaemia. Univariate and multivariate logistic regression models were used to determine the potential predictors of overweight, obesity and central obesity, and adjusted odds ratios (AOR) were obtained. Incidence rate of overweight, obesity and central obesity was reported among those who had none of these outcomes in phase 1. RESULTS: The prevalence was 35.8% (37% men, 35% women) for overweight, 22.3% (16% men, 26.3% women) for obesity, and 31.1% (15.6% men, 41.2% women) for central obesity. The prevalence of overweight/obesity was significantly associated with age (AOR = 2.8-7.4), higher education (AOR = 1.7), female gender (AOR = 1.4), low physical activity (AOR = 1.3), smoking (AOR = 0.55) and opium use (AOR = 0.79). The prevalence increased from 33.3% to 35.8% for overweight and from 15.4% to 22.3% for obesity between phases 1 and 2. The incidence rate per 100 person-years was 5.5 for overweight, 4.7 for obesity and 2.9 for central obesity. CONCLUSION: Prevalence of overweight and obesity increased over 5 years. Middle-aged participants, women, and those with low physical activity were at higher risk for overweight/obesity.

Cisplatin-Induced Nephrotoxicity; Protective Supplements and Gender Differences

Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.

Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in ovariectomized estradiol treated rats.

The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR) or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500 µg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF), and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (Pdose <0.001) and A779-treated (Pdose <0.01) animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05). When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats.

Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg(-1) min(-1)) were determined. Results. Percentage change of RBF (%RBF) in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P < 0.05). Infusion of 300 ng kg(-1) min(-1) Ang 1-7 increased RBF by 6.9 ± 1.9% in OVE group versus 0.9 ± 1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.