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    Topical application of metformin accelerates cutaneous wound healing in streptozotocin-induced diabetic rats
    (Springer Link, 2021) Tombultürk, Fatma Kübra; Todurga-Seven, Zeynep Gizem; Hüseyinbaş, Önder; Özyazgan, Sibel; Turgut, Ulutin; Kanigur-Sultuybek, Gönül
    Background: Diabetic chronic wound, which is one of the diabetic complications caused by hyperglycemia, characterized by prolonged inflammation has become one of the most serious challenges in the clinic. Hyperglycemia during diabetes not only causes prolonged inflammation and delayed wound healing but also modulates the activation of nuclear factor-kappa B (NF-?B) and the expression of matrix metalloproteinases (MMPs). Although metformin is the oldest oral antihyperglycemic drug commonly used for treating type 2 diabetes, few studies have explored the molecular mechanism of its topical effect on wound healing. Therefore, we aimed to investigate the molecular effects of topical metformin application on delayed wound healing, which's common in diabetes. Methods and results: In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-?B p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline. As a result of our study, we showed that topically applied metformin accelerates wound healing by suppressing NF-?B p65 activity and diminishing the expression of MMP2 and MMP9. Conclusions: Diabetic wounds treated with metformin healed even faster than those in the control group that mimicked standard wound healing.