Protective effect of glyburide on wound healing in streptozotocin-induced diabetic rats via alteration of NF-κB/transforming growth factor-β and cellular jun/platelet-derived growth factor-vascular endothelial growth factor signaling pathways

BACKGROUND: Diabetes-induced abnormal wound healing is characterized by prolonged oxidative stress, inflammation, and impaired tissue regeneration, largely due to excessive production of oxidative stress and inflammatory mediators. Glyburide is a well-known antidiabetic drug. In this experimental study, we scrutinized the protective effect of glyburide against streptozotocin (STZ) induced wound healing in rats and explored the underlying mechanism. MATERIALS AND METHODS: Swiss Wistar rats were randomly assigned to groups and intraperitoneally injected with STZ to induce diabetes. The rats received the oral administration of glyburide (1.25, 2.5, and 5 mg/kg). We estimated the wound area, body weight, glucose level, insulin level, food intake, water intake, protein, albumin, glucosamine, hydroxyproline, collagen, macrophage migration inhibitory factor (MIF), hexosamine, lipid parameters, antioxidant parameters, apoptosis parameters, inflammatory cytokines, and inflammatory parameters. The mRNA expression levels were estimated in the rats' skin. RESULTS: Dose-dependent treatment of glyburide decreased the wound area, glucose level, food intake, and water intake, and enhanced the body weight and insulin. Glyburide treatment altered the level of protein, albumin, glucosamine, hydroxyproline, collagen, MIF, hexosamine, lipid parameters (total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein, very LDL), oxidative stress (malonaldehyde, glutathione, glutathione peroxidase, superoxide dismutase, and catalase), inflammatory cytokines (tumor necrosis factor-α, interleukin-1 β (IL-1 β), IL-6, IL-10, and IL-17), apoptosis parameters (B-cell lymphoma 2 [Bcl-2]-associated X protein [Bax], Bcl-2, cysteine-aspartic acid protease 3 [caspase-3]), inflammatory parameters (cyclooxygenase-2, prostaglandin (PGE2), inducible nitric oxide synthase, nuclear kappa B factor (NF-κB), transforming growth factor-β [TGF-β]). Glyburide treatment altered the mRNA expression of cellular jun (c-Jun), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), chemokine-1 (CXCL1), chemokine-2 (CXCL2), tyrosine kinase with immunoglobulin-like and EGF-like domains Tyrosine Kinase (Tie-2), angiopoietin-1, mothers against decapentaplegic homolog 2 and 3 (Smad2/3), and Transforming growth factor-beta (TGF-β). CONCLUSION: The result clearly showed the protective effect of glyburide against STZ-induced diabetic wound via alteration of NF-κB/TGF-β and c-Jun/PDGF-VEGF Signaling Pathways.