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: Serap Sancar-Bas, Selda Gezginci-Oktayoglu, Sehnaz Bolkent
• Journal: Growth factors (Chur, Switzerland) (Growth Factors) Vol. 33 Issue 5-6 Pg. 419-29 ( 2015) ISSN: 1029-2292 [Electronic] England
• PMID: 26728502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2
• Icam1 protein, mouse
• Peptides
• Proliferating Cell Nuclear Antigen
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Venoms
• Intercellular Adhesion Molecule-1
• Streptozocin
• Exenatide
• L-Lactate Dehydrogenase
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Chemokine CCL2 (biosynthesis)
• Diabetes Mellitus, Experimental
• Diabetic Nephropathies (drug therapy)
• Exenatide
• Inflammation (drug therapy)
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Kidney Tubules (drug effects, injuries)
• L-Lactate Dehydrogenase (metabolism)
• Macrophages (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Oxidative Stress (drug effects)
• Peptides (therapeutic use)
• Proliferating Cell Nuclear Antigen (metabolism)
• Reactive Oxygen Species (metabolism)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Streptozocin
• Tumor Necrosis Factor-alpha (metabolism)
• Venoms (therapeutic use)