Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus. Academic Article uri icon

abstract

  • Clinical trials have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcomes in diabetes mellitus (DM) patients. As most studies were performed in Type 2 DM, the cardiovascular effects of SGLT2 inhibition still require clarification in Type 1 DM. We analyzed the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 DM. Methods: Male Wistar rats were assigned into four groups: control (C, n = 14); control treated with dapagliflozin (C + DAPA, n = 14); diabetes (DM, n = 20); and diabetes treated with dapagliflozin (DM + DAPA, n = 20) for 8 weeks. Dapagliflozin dosage was 5 mg/kg/day. Statistical analyses: ANOVA and Tukey or KruskalWallis and Dunn. Results: DM + DAPA presented decreased blood pressure and glycemia and increased body weight compared to DM (C 507 52; C + DAPA 474 50; DM 381 52 *; DM + DAPA 430 48 # g; * p < 0.05 vs. C; # p < 0.05 vs. C + DAPA and DM + DAPA). DM echocardiogram presented left ventricular and left atrium dilation with impaired systolic and diastolic function. Cardiac changes were attenuated by dapagliflozin. Myocardial hydroxyproline concentration and interstitial collagen fraction did not differ between groups. The expression of Type III collagen was lower in DM and DM + DAPA than their controls. Type I collagen expression and Type I-to-III collagen ratio were lower in DM + DAPA than C + DAPA. DM + DAPA had lower lipid hydroperoxide concentration (C 275 42; C + DAPA 299 50; DM 385 54 *; DM + DAPA 304 40 # nmol/g tissue; * p < 0.05 vs. C; # p < 0.05 vs. DM) and higher superoxide dismutase and glutathione peroxidase activity than DM. Advanced glycation end products did not differ between groups. Conclusion: Dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental rat model of Type 1 diabetes mellitus.

published proceedings

  • Antioxidants (Basel)

author list (cited authors)

  • Rosa, C. M., Campos, D., Reyes, D., Damatto, F. C., Kurosaki, L. Y., Pagan, L. U., ... Okoshi, K.

citation count

  • 4

complete list of authors

  • Rosa, Camila Moreno||Campos, Dijon Henrique Salome||Reyes, David Rafael Abreu||Damatto, Felipe Cesar||Kurosaki, Lucas Yamada||Pagan, Luana Urbano||Gomes, Mariana Janini||CorrĂȘa, Camila Renata||Fernandes, Ana Angelica Henrique||Okoshi, Marina Politi||Okoshi, Katashi

publication date

  • May 2022

publisher