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Inhibition of the Sodium‐Glucose Co‐Transporter Protein Type 2 Decreases Oxidative Stress and Improves Cardiac Remodeling in Rats with Diabetes Mellitus
Author(s) -
Rosa Camila Moreno,
Campos Dijon Henrique Salome,
Reyes David Rafael,
Pagan Luana Urbano,
Gomes Mariana Janini,
Damatto Felipe,
Fernandes Ana Angélica Henrique,
Okoshi Marina Politi,
Okoshi Katashi
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb570
Subject(s) - dapagliflozin , medicine , endocrinology , oxidative stress , renal glucose reabsorption , streptozotocin , type 2 diabetes mellitus , diabetes mellitus , chemistry , pharmacology
Purpose A new class of antidiabetic drugs aims to inhibit the sodium‐glucose co‐transporter type 2 (SGLT2). Thus, SGLT2 inhibition results in a reduction of hyperglycemia by decreasing reabsorption of glucose and increasing urinary excretion. Therefore, this study aimed to analyze the effects of SGLT2 inhibition by dapagliflozin (DAPA) on cardiac remodeling in rats with diabetes mellitus (DM). Methods Male Wistar rats with 450 g were divided into four groups: control (CTL, n=15); CTL+DAPA (n=15); DM (n=15); DM+DAPA (n=15). Diabetes was induced by streptozotocin (40 mg/kg, i.p., single dose). CTL+DAPA and DM+DAPA groups received DAPA (5 mg/kg/day, added to the rat chow) for 8 weeks. In vivo cardiac structures and functions were assessed by echocardiogram. Oxidative stress was evaluated in left ventricular myocardial tissue by measuring the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), catalase, and lipid hydroperoxide (LPO). Statistics Comparisons were performed by ANOVA ‐ 2×2 factorial (p<0.05). Results Compared to the DM group, DM+DAPA group presented higher body weight (DM: 343±52; DM+DAPA: 389±46 g; p<0.05), lower blood glucose (DM: 487±80; DM+DAPA: 172±89 mg/dL; p<0.05), and lower systolic blood pressure (DM: 140±7; DM+DAPA: 133±7 mmHg; p<0.05). Echocardiography showed lower left ventricular (LV) and left atrial diameter, and improved LV systolic and diastolic function in DM+DAPA compared to the DM group. Activities of SOD (DM: 13.7±3.90; DM+DAPA: 23.5±4.12 nmol/mg protein; p<0.05), GSH‐Px (DM: 19.7±5.07; DM+DAPA: 33.5±6.84 nmol/mg tissue; p<0.05), and catalase (DM: 85.4±23.0; DM+DAPA: 117±20.1 μmol/g tissue; p<0.05) were increased, and LPO levels (DM: 385±53.8; DM+DAPA: 304±39.8 nmol/g tissue; p<0.05) decreased in the DM+DAPA, compared to the DM group. Conclusion Inhibition of the sodium‐glucose co‐transporter type 2 by dapagliflozin decreases oxidative stress and improves cardiac remodeling in rats with diabetes mellitus. Support or Funding Information FAPESP, and CNPq.