Name: LEONARDO DA SILVA ESCOUTO
Publication date: 25/04/2024
Examining board:
Name |
Role |
|---|---|
| BIANCA PRANDI CAMPAGNARO | Examinador Externo |
| ROGER LYRIO DOS SANTOS | Examinador Interno |
Summary: Introduction: Arterial hypertension is a chronic condition characterized by increased blood pressure, being a major risk factor for cardiovascular diseases (CVD), chronic kidney disease (CKD), and premature death worldwide. It can be exacerbated by comorbidities such as dyslipidemia, obesity, glucose intolerance, and diabetes mellitus. Additionally, in the postmenopausal phase, ovarian hormone deficiency can accelerate the progression of these comorbidities, with sex hormones such as estrogen being essential for renal tissue protection. On the other hand, hormonal replacement therapy in the postmenopausal phase is controversial, with studies pointing to health risks. Therefore, non-pharmacological therapies, such as the probiotic Kefir, which has antioxidant, anti-inflammatory, and antihypertensive effects, could be used as adjuvant therapy to prevent or control renal alterations in postmenopausal women, without the risks associated with traditional hormonal therapy. Objective: To evaluate the effect of Kefir treatment on renal function in an experimental model of metabolic syndrome and ovarian hormone deficiency, using female SHR rats with fructose overload. Materials and Methods: Young female SHR rats at 8 weeks of age and weighing approximately 130g, were used. They were divided into 4 groups (n: 7): Ovariectomized (OVX) control (O); OVX Fructose (OF); OVX Kefir (OK); and OVX Kefir + Fructose (OKF). The animals were treated for 8 weeks with Kefir (5% w/v) via gavage, and Fructose (10% w/v) was diluted in water ad libitum. The following parameters were evaluated: body weight and other morphometric parameters; fasting blood glucose and glucose tolerance test (GTT); metabolic cage; renal function (GFR; RPF; RBF and RVR); serum and urine biochemical parameters (urea, creatinine and microalbuminuria); Total Nitric Oxide (NOx) bioavailability (Griess Method); superoxide anion (DHE), hydrogen peroxide (DCF) and peroxynitrite (HPF); lipid peroxidation (TBARS) and advanced protein oxidation products (AOPP); renal remodeling (Picrosirius Red). Data were analyzed using GraphPad Prism 8, presented as mean ± SEM, analyzed by one or two-way ANOVA, followed by Fischer's post hoc test, with p < 0.05 considered significant. This project was approved by the CEAU-UFES (protocol n.11/2019). Results: The groups exposed to fructose (OF and OKF) showed an increase in Weight (O: 65.14 ± 3.11; OF: 90.29 ± 5.87; OK: 71.43 ± 4.29; OKF: 95.00 ± 5.28) and visceral fat (O: 2.86 ± 0.38; OF: 5.29 ± 0.93; OK: 2.92 ± 0.41; OKF: 5.63 ± 0.94). Besides that, OF and OKF showed an increase in fasting blood glucose (O: 72.00 ± 3.25; OF: 101.4 ± 2.58; OK: 78.80 ± 2.13; OKF: 109.8 ± 3.38). Although OF also showed a higher glycemic peak in the glucose tolerance test (GTT) response, OKF partially reduced this parameter, as evidenced by the area under the curve (AUC) (O: 14885 ± 690; OF: 20880 ± 908; OK: 14427 ± 369; OKF: 17967 ± 1076). Regarding renal function, the results show that OF and OKF groups had a reduction in GFR (O: 4.72 ± 0.15; OF: 3.45 ± 0.25; OK: 4.57 ± 0.33; OKF: 3.16 ± 0.35), indicating that Kefir was not able to prevent the damage caused by fructose. Furthermore, in RPF (O: 7.97 ± 0.81; OF: 7.75 ± 0.77; OK: 7.90 ± 0.52; OKF: 13.84 ± 0.65) and RBF (O: 13.20 ± 1.28; OF: 12.62 ± 1.22; OK: 13.28 ± 0.82; OKF: 24.82 ± 1.49) no significant differences were found between OF, OK and control group. Meanwhile, there was a significant increase in OKF compared to the other groups in both parameters. Moreover, the RVR (O: 12.39 ± 1.20; OF: 10.37 ± 0.49; OK: 11.72 ± 1.03; OKF: 6.19 ± 0.30), which is inversely proportional to the RBF, showed a significant reduction in the OKF group compared to the other groups. Finally, this increase in flow parameters and reduction in renal resistance in OKF are possibly related to the increase in NOx (O: 2.19 ± 0.20; OF: 2.63 ± 0.14; OK: 3.81 ± 0.38; OKF: 3.28 ± 0.14), and reduction in hydrogen peroxide (O: 176.7 ± 21.24; OF: 289.7 ± 26.49; OK: 240.6 ± 22.77; OKF: 187.7 ± 24.67) and peroxynitrite (O: 138.9 ± 35.91; OF: 157.2 ± 15,30; OK: 149.8 ± 51.63; OKF: 98.84 ± 28.77). As well as, the significant reduction in microalbuminuria (O: 77.20 ± 11.71; OF: 116.2 ± 7.341; OK: 88.00 ± 5.099; OKF: 44.50 ± 4.039) in OKF group. Conclusion: In the present study, Kefir showed favorable effects in the model of metabolic syndrome and ovarian hormone deficiency (OKF), potentially protecting the kidney from the deleterious effects of fructose. On the whole, Kefir may act as a significant adjunct for preventive treatment in clinical situations similar to the experimental model studied.
