Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus
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 effec...
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MDPI AG
2022-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/5/982 |
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| author | Camila Moreno Rosa Dijon Henrique Salome Campos David Rafael Abreu Reyes Felipe Cesar Damatto Lucas Yamada Kurosaki Luana Urbano Pagan Mariana Janini Gomes Camila Renata Corrêa Ana Angelica Henrique Fernandes Marina Politi Okoshi Katashi Okoshi |
| author_facet | Camila Moreno Rosa Dijon Henrique Salome Campos David Rafael Abreu Reyes Felipe Cesar Damatto Lucas Yamada Kurosaki Luana Urbano Pagan Mariana Janini Gomes Camila Renata Corrêa Ana Angelica Henrique Fernandes Marina Politi Okoshi Katashi Okoshi |
| author_sort | Camila Moreno Rosa |
| collection | DOAJ |
| description | 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, <i>n</i> = 14); control treated with dapagliflozin (C + DAPA, <i>n</i> = 14); diabetes (DM, <i>n</i> = 20); and diabetes treated with dapagliflozin (DM + DAPA, <i>n</i> = 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; * <i>p</i> < 0.05 vs. C; # <i>p</i> < 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; * <i>p</i> < 0.05 vs. C; # <i>p</i> < 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. |
| first_indexed | 2024-03-10T03:25:51Z |
| format | Article |
| id | doaj.art-eb3e76d2178b477b870bf9f6c2780864 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T03:25:51Z |
| publishDate | 2022-05-01 |
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| series | Antioxidants |
| spelling | doaj.art-eb3e76d2178b477b870bf9f6c27808642023-11-23T09:52:37ZengMDPI AGAntioxidants2076-39212022-05-0111598210.3390/antiox11050982Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes MellitusCamila Moreno Rosa0Dijon Henrique Salome Campos1David Rafael Abreu Reyes2Felipe Cesar Damatto3Lucas Yamada Kurosaki4Luana Urbano Pagan5Mariana Janini Gomes6Camila Renata Corrêa7Ana Angelica Henrique Fernandes8Marina Politi Okoshi9Katashi Okoshi10Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilDepartment of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilDepartment of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilDepartment of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilDepartment of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilDepartment of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilBrigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, BrazilDepartment of Chemistry and Biochemistry, Institute of Biosciences, Sao Paulo State University, UNESP, Botucatu 18618-970, SP, BrazilDepartment of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilDepartment of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu 18618-687, SP, BrazilClinical 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, <i>n</i> = 14); control treated with dapagliflozin (C + DAPA, <i>n</i> = 14); diabetes (DM, <i>n</i> = 20); and diabetes treated with dapagliflozin (DM + DAPA, <i>n</i> = 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; * <i>p</i> < 0.05 vs. C; # <i>p</i> < 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; * <i>p</i> < 0.05 vs. C; # <i>p</i> < 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.https://www.mdpi.com/2076-3921/11/5/982SGLT2 inhibitorventricular remodelingoxidative stressmyocardial fibrosisdapagliflozincardiac function |
| spellingShingle | Camila Moreno Rosa Dijon Henrique Salome Campos David Rafael Abreu Reyes Felipe Cesar Damatto Lucas Yamada Kurosaki Luana Urbano Pagan Mariana Janini Gomes Camila Renata Corrêa Ana Angelica Henrique Fernandes Marina Politi Okoshi Katashi Okoshi Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus Antioxidants SGLT2 inhibitor ventricular remodeling oxidative stress myocardial fibrosis dapagliflozin cardiac function |
| title | Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus |
| title_full | Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus |
| title_fullStr | Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus |
| title_full_unstemmed | Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus |
| title_short | Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus |
| title_sort | effects of the sglt2 inhibition on cardiac remodeling in streptozotocin induced diabetic rats a model of type 1 diabetes mellitus |
| topic | SGLT2 inhibitor ventricular remodeling oxidative stress myocardial fibrosis dapagliflozin cardiac function |
| url | https://www.mdpi.com/2076-3921/11/5/982 |
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