Dapagliflozin, a sodium glucose cotransporter 2 inhibitors, protects cardiovascular function in type-2 diabetic murine model

• Published in: Journal of genetics 2020-12, Vol.99 (1), Article 46
• Main Authors: Saleh, Sohair, Hanna, Gergess, El-Nabi, Sobhy Hassab, El-domiaty, Heba, Shabaan, Anwaar, Ewida, Suzy Fayez
• Format: Article
• Language: English
• Subjects: Animal Genetics and Genomics; Animal models; Animals; Antidiabetics; Antioxidants; Aorta; Benzhydryl Compounds - pharmacology; Biomedical and Life Sciences; Blood Glucose - analysis; Blood pressure; Cardiovascular diseases; Cardiovascular system; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Collagen; Dapagliflozin; Deoxyribonucleic acid; Dextrose; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes therapy; Diet, High-Fat; Disease Models, Animal; DNA; DNA fragmentation; Ethylenediaminetetraacetic acid; Evolutionary Biology; Genomics; Glucose; Glucosides - pharmacology; Glycemic index; Heart; Inflammation; Life Sciences; Malondialdehyde; Metformin; Microbial Genetics and Genomics; Nitric-oxide synthase; Oxidative stress; Plant Genetics and Genomics; Random Allocation; Rats; Research Article; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Triglycerides - blood; Tumor necrosis factor; Tumors; Type 2 diabetes
• ISSN: 0022-1333; 0973-7731
• DOI: 10.1007/s12041-020-01196-9

Diabetes mellitus and its complications are major international health problems in which there are many limitations to the orthodox approaches in the treatment. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetic medications, with a different mechanism of action that may reduce risk of cardiovascular complications. To evaluate the effect of SGLT2 inhibitor monotherapy on cardiovascular complications in patients with type-2 diabetes and to compare its effect with the first-line therapy, metformin. Eighty rats divided into four groups were used: nondiabetic, diabetic nontreated, diabetic + met and diabetic + dapa. At the end, the arterial blood pressure and cardiac performance were assessed. Glycemic index, lipid profile, total antioxidant capacity, malondialdehyde, tumour necrosis factor α were measured. DNA changes were assessed from the hearts and aortae. Aortic tissue changes recorded using haematoxylin and eosin, Masson trichrome and iNOS immune stain. Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflozin treated groups with significant improvement in blood pressure and cardiac performance. Also, there were noticeable significant reduction in DNA fragmentation in aortic and cardiac tissues and reduction in collagen deposition and iNOS expression in aortic tissue. Dapagliflozin treatment results’ significantly surpassed improvement of metformin treatment nearly in all parameters. Total genomic DNA extraction proved that SGL2 inhibitor (dapagliflozin) has superior glycemic control and cardiovascular protective effect over metformin especially in type-2 diabetes with high fat intake.