title: Exendin-4 attenuates renal tubular injury by decreasing oxidative stress and inflammation in streptozotocin-induced diabetic mice.
abstract: In this study, we aimed to research the restorative effects of exendin-4, a GLP-1 analog, on renal tubular injury in streptozotocin-induced diabetes model. BALB/c male mice were divided into four groups: non-diabetic, non-diabetic + exendin-4 (3 μg/kg), diabetic and diabetic + exendin-4. In our diabetic model, we observed renal injury mainly in tubular area rather than glomeruli and exendin-4 decreased tubular injury with its glucose lowering effect. Besides, PCNA positive tubular cells, activities of LDH and Na(+)-K(+)-ATPase were also significantly declined by the administration of exendin-4. Furthermore, exendin-4 attenuated the levels of ROS, MDA, 8-OHdG, proinflammatory cytokines (TNF-α, IL-1β), chemokine MCP-1, ICAM-1, and fibrosis-related molecules (transforming growth factor β1 and fibronectin). In consistent with reducing tubular injury, macrophage infiltration and both MCP-1 and ICAM-1 production in tubular cells were decreased. These results indicate that exendin-4 may decrease renal tubular injury seen in the beginning of diabetic nephropathy by decreasing ROS production and inflammation.
authors.affiliation: a Biology Department, Molecular Biology Section , Faculty of Science, Istanbul University , Istanbul , Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Sancar-Bas
authors.affiliation: a Biology Department, Molecular Biology Section , Faculty of Science, Istanbul University , Istanbul , Turkey.
authors.forename: Selda
authors.initials: S
authors.lastname: Gezginci-Oktayoglu
authors.affiliation: a Biology Department, Molecular Biology Section , Faculty of Science, Istanbul University , Istanbul , Turkey.
authors.forename: Sehnaz
authors.initials: S
authors.lastname: Bolkent
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D000077270:Exenatide; D007249:Inflammation / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007684:Kidney Tubules / Q000187:drug effects* / Q000293:injuries; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014688:Venoms / Q000627:therapeutic use*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C090509:Icam1 protein, mouse; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014688:Venoms; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin; D000077270:Exenatide; D007770:L-Lactate Dehydrogenase; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Diabetic nephropathy; exendin-4; inflammation; oxidative stress; renal tubular injury