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

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

• Tipo de documento: Artigo Científico
• Fonte: ANTIOXIDANTS; v. 11, n. 5, p. 14-pg., 2022-05-01.

Resumo

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 Kruskal-Wallis 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. (AU)

• Processo FAPESP: 18/00567-4 - Influência da empaglifozina sobre o coração de ratos normais e com remodelação cardíaca induzida por infarto do miocárdio
• Beneficiário: Katashi Okoshi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/02324-3 - Efeitos do bloqueio da proteína cotransportadora de sódio-glicose tipo 2 no coração de ratos com diabetes mellitus
• Beneficiário: Camila Moreno Rosa Bassetto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado