Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Physiology

Background: Diabetes has become a widespread epidemic, including the increasing prevalence and incidence of type 1 diabetes. Diabetic nephropathy (DN) is a common complication of diabetes. In recent years, mesenchymal stromal cells (MSCs) have been highlighted as a new emerging regenerative therapy due to their multipotency, and paracrine secretion of angiogenic factors, cytokines, and immunomodulatory substances. MSCs may also have glucose lowering properties providing another attractive and unique feature of this therapeutic approach. MSC administration has significant potential in the treatment of DN but challenges remain in terms of engraftment, persistence, and tissue targeting. Melatonin seems to regulate signaling pathways that drive differentiation of MSC into different tissues. Objective: This study tried to evaluate the effects of melatonin or stem cells (especially those attenuated with melatonin) on streptozotocin induced DN in type 1 diabetic male rats. Methods: sixty adult male albino rats were divided into: Control group (I), diabetic group (II), diabetic + melatonin (III) group given melatonin intraperitoneal for 2 weeks after induction of diabetes, diabetic + stem cells (IV) group treated with stem cells a single dose by intravenous injection in rat tail vein after induction of diabetes and diabetic + stem cells attenuated with melatonin (V) group treated with stem cells after attenuation with melatonin ex vivo after induction of diabetes. At the end of the study period, GFR, BP, serum fasting blood glucose, serum insulin, plasma and urine creatinine level, Urea, urinary albumin excretion (UAE), serum angiotensin level, carboxymethyl lysine, kidney tissue level of : (tumor necrosis factor-alpha (TNF-Ü), Interleukin10 (IL- 10), Basic fibroblast growth factor (b-FGF), Super oxide dismutase), and glomerular expression of (TGF-Ý, Bcl-2, Beclin) were measured

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