Clarification of reproductive and cardiotoxic potentials and mechanism of Dapagliflozin in repeated exposure

Dapagliflozin, Sodium-Glucose co-transporter 2 inhibitor, is an antidiabetic drug that aims to control hyperglycemia with its insulin independent effect by providing glucose excretion from the kidney, different from other antidiabetic drug groups. Dapagliflozin shows the effects via urinary glucose excretion and decrease blood glucose levels, HbA1c values, hypertension and insulin resistance. It causes adverse effects such as orthostatic hypotension, dehydration, urinary tract and genital infections caused by glycosuria. As a result of case studies, clinical trials and in vivo studies, drug-related adverse reactions are frequently updated, so Dapagliflozin is among the drugs that are subject to additional monitoring. In this study, diabetes was induced by streptozotocin in 250-300 g young adult male Sprague-Dawley rats. Dapagliflozin (10 mg/kg) was given by oral gavage to diabetic rats for 28 days. After the animals were sacrificed on the 28th day, biochemical and hormonal analyzes in plasma, histological examinations in the heart and testicles, and sperm counting and morphological examination were performed. The data obtained were evaluated by one-way ANOVA. As a result of this study, with the diabetes development in animals, (i) reproductive system damage such as induction of apoptosis in the seminiferous tubules, changes in testis and sperm morphology and formation of oxidative damage; (ii) disordered myocardial cells and rupture of myocardial fibers and in the heart, formation of oxidative damage was observed. (iii) These damages were found to be lower and close to the control group in diabetic animals treated with DAPA. DAPA did not have a significant toxic effect on the male reproductive system and the cardiovascular system. It is believed that the results obtained will contribute to the literature in terms of the risks and possible effects of DAPA.