الفهرس 
Early detection of experimental diabetic nephropathy and the prognostic impact of certain ant diabetic drugs
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Abstract
Early detection and clinical interference are major challenges for the prevention of diabetic nephropathy (DN) progression. This study aimed to detect early signs of DN and study the potential ameliorating effect of dapagliflozin, a sodium glucose co-transporter 2 inhibitor, and linagliptin, a dipeptidyl peptidase-4 inhibitor, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetes in rats. Fr-STZ rats were treated with either dapagliflozin (1 mg/kg p.o. daily), linagliptin (3 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks. Fr-STZ rats displayed marked early tubular renal damage and glomerular podocyte injury as evidenced by renal KIM-1, NGAL, cystatin C, and vanin-1 mRNA, as well as urinary NAG elevation and nephrin mRNA suppression, associated with the development of marked renal interstitial fibrosis and glomerulosclerosis despite the presence of normoalbuminuria. Propagation of oxidative, inflammatory, fibrotic, and apoptotic reactions was obvious in the setting of renal glucose overload. Dapagliflozin or linaglitpin significantly attenuated the renal tubular injury makers namely KIM-1, NGAL, vanin-1 and urinary NAG. In addition, they restored glomerular nephrin expression and reversed renal histopathological changes. Oxidative, inflammatory, and fibrotic processes were also alleviated. This study suggests that dapagliflozin or linagliptin exerts a renoprotective effect against early features of DN in rats presumably by preventing diabetes-induced early tubular and glomerular podocyte damage thereby inhibiting KIM-1 and NGAL associated with renal tubular inflammation and fibrosis together with hampering vanin-1-mediated renal oxidative stress-induced podocyte nephrin injury, apoptosis, and loss