Garlic (Allium Sativum) Modulates The Expression Of The Receptor For Advanced Glycation End Product (Rage) Isoforms In Renal Tissues Of Streptozotocin-Induced Diabetic Rats

Background The up-regulation of the receptor for advanced glycation end products (RAGE) has been implicated as a major mediator in the development and progression of diabetic nephropathy. Objective The present study was designed to investigate the potential of garlic to modulate the level of expression of RAGE in renal tissues of diabetic rats. Method Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. Results A polyclonal antibody of proven specificity to RAGE indicated in immunohistochemical assays that RAGE labeling was significantly increased in renal tissues of control diabetic rats compared to the normal group. The increased RAGE labeling involved mesangial cells in the majority of glomeruli, which also exhibited signs of mesangial expansion, mesangial nodule formation and glomerulosclerosis. In 2-dimensional Western blots, RAGE expression in renal tissues was dominated by a heterogeneous group of charge variants, represented by 46-50 kDa isoforms with an obvious shift towards more basic pIs compared to their counterparts in normal rats. Compared to control diabetic rats, RAGE labeling in the garlic-treated diabetic group was significantly reduced throughout renal regions and was marked by the expression of 43-50 kDa acidic charge variants comparable to those observed in normal rats. Conclusion The capacity of garlic to modulate diabetes-induced up-regulation of selective RAGE polymorphic variants may be implicated in attenuating the detrimental consequences of excessive RAGE signaling manifested by diabetes-associated disorders.