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Dapagliflozin attenuates cardiac remodeling in rats with diabetes mellitus
Session:
Posters 4 - Écran 04 - Insuficiência Cardíaca
Speaker:
Camila Moreno Rosa Bassetto
Congress:
CPC 2018
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.2 Basic Science - Cardiac Biology and Physiology
Session Type:
Posters
FP Number:
---
Authors:
Camila Moreno Rosa ; Dijon Henrique Salomé de Campos; David Rafael Abreu Reyes; Luana Urbano Pagan; Mariana Janini Gomes; Felipe César Damatto; Ana Angélica Henrique Fernandes; Marina Politi Okoshi; Katashi Okoshi
Abstract
<p><strong>Purpose:</strong> A new class of antidiabetic drugs, the sodium-glucose co-transporter protein type 2 (SGLT2) blocker, cause decrease of hyperglycemia by reducing reabsorption of glucose and increasing its urinary excretion. The aim of this study was to analyze the effects of SGLT2 blockade by dapagliflozin (DAPA) on cardiac remodeling in diabetic rats. <strong>Methods: </strong>Male Wistar rats with 450 g were divided into four groups: control (CTL, n=15); CTL+DAPA (n=15); diabetes mellitus (DM, n=15); DM+DAPA (n=15). Diabetes were induced by streptozotocin (40 mg/kg, i.p., single dose). CTL+DAPA and DM+DAPA groups received DAPA (5 mg/kg/day, added in the chow) for 8 weeks. Cardiac structures and functions were assessed by echocardiogram. Oxidative stress was evaluated in cardiac tissue by activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase, and lipid hydroperoxide (LPO) concentration. Myocardial collagen analysis was performed by quantification of hydroxyproline and Western Blot (collagens type I, III and lysyl oxidase). Cardiomyocytes diameter and interstitial collagen fraction were measured in left ventricle (LV) histological sections <strong>Statistics:</strong> Comparisons were performed by ANOVA (p<0.05). <strong>Results: </strong>Compared to the DM group, DM+DAPA group presented higher body weight (389±46 vs. 343±52 g), lower blood glucose (172±89 vs. 487±80 mg/dL), and lower systolic blood pressure (133±7 vs. 140±7 mmHg). Echocardiography showed lower LV and left atrial diameters, and better LV systolic and diastolic functions in DM+DAPA compared to DM group. Activity of antioxidant enzymes was increased in DM+DAPA compared to DM groups (SOD: 23.5±4.12 vs. 13.7±3.90 nmol/mg protein, p<0.05; GSH-Px: 33.5±6.84 vs. 19.7±5.07 nmol/mg tissue, p<0.05; and catalase: 117±20.1 vs. 85.4±23.0 µmol/g tissue, p<0.05), and LPO was decreased in DM+DAPA compared to DM group (304±40 vs. 385±54 nmol/g tissue, p<0.05). Regarding to the evaluation of myocardial collagen and histological analysis, we did not observe significant difference between the groups. <strong>Conclusion: </strong>Blockade of sodium-glucose co-transporter protein type 2 by dapagliflozin decreases the oxidative stress and improves cardiac remodeling in rats with diabetes mellitus. </p> <p> </p>
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