AUTHOR=El-Shafey Mohamed , El-Agawy Mosaab Salah El-din , Eldosoky Mohamed , Ebrahim Hasnaa Ali , Elsherbini Dalia Mahmoud Abdelmonem , El-Sherbiny Mohamed , Asseri Saad Mohamed , Elsherbiny Nehal M. 

TITLE=Role of Dapagliflozin and Liraglutide on Diabetes-Induced Cardiomyopathy in Rats: Implication of Oxidative Stress, Inflammation, and Apoptosis

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.862394

DOI=10.3389/fendo.2022.862394

ISSN=1664-2392

ABSTRACT=The current study aims to assess protective effects of dapagliflozin (a sodium glucose cotransporter-2 inhibitor, Dapa) and/or liraglutide (a glucagon-like peptide 1 agonist, Lira) in experimental model of diabetic cardiomyopathy (DCM). Single dose of streptozotocin (STZ) was administrated to male Sprague Dawley rats by intraperitoneal injection at a dose of 50 mg/kg to induce diabetes mellitus.   Dapa (1 mg/kg, orally), Lira (0.4 mg/kg, s.c.) and Dapa-Lira combination were administrated for 8 weeks once-daily. Blood samples were evaluated for glucose level and biochemical markers of cardiac functions. Cardiac tissue were dissected and assessed for redox homeostasis (MDA, GSH and CAT), pro-inflammatory mediators (NF-κB, TNF-α) and apoptotic effectors (Caspase-3). Moreover, effect of treatments on cardiac cellular structure was studied. Dapa and/or Lira administration resulted in significant improvement of biochemical indices of cardiac function. Additionally, all treatment groups demonstrated restoration of oxidant/antioxidant balance. Moreover, inflammation and apoptosis key elements were markedly down-regulated in cardiac tissue. Also, histological studies demonstrated attenuation of diabetes-induced cardiac tissue injury. Interestingly, Dapa-Lira combination treatment produced more favourable protective effect compared to single treatment. These data demonstrated that Dapa, Lira and their combination therapy could useful in protection against DM-accompanied cardiac tissue injury, shedding the light on their possible utilization as adjuvant therapy for management of DM patients