Mechanisms of ivermectin-induced wound healing
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RESEARCH ARTICLE
Open Access
Mechanisms of ivermectin-induced wound healing Daniel Kwesi Sia1,2, Kwesi Boadu Mensah1* , Tony Opoku-Agyemang2, Raphael D. Folitse2 and David Obiri Darko1
Abstract Background: Wounds cause structural and functional discontinuity of an organ. Wound healing, therefore, seeks to re-establish the normal morphology and functionality through intertwined stages of hemostasis, inflammation, proliferation, and tissue remodelling. Ivermectin, a macrolide, has been used as an endectoparasiticide in human and veterinary medicine practice for decades. Here, we show that ivermectin exhibits wounding healing activity by mechanisms independent of its well-known antiparasitic activity. This study aimed to evaluate the wound healing property of ivermectin cream using histochemistry and enzyme-linked immunosorbent assay techniques. Results: Non-irritant dose of ivermectin cream (0.03–1%) decreased wound macroscopic indices such as exudation, edge edema, hyperemia, and granulation tissue deposition by day 9 compared to day 13 for the vehicle-treated group. This corresponded with a statistically significant wound contraction rate, hydroxyproline deposition, and a decreased time to heal rate. The levels of growth factors TGF-β1 and VEGF were significantly elevated on day 7 but decreased on day 21. This corresponded with changes in cytokines (IL-1α, IL-4, IL-10, and TNF-α) and eicosanoids (LTB4, PGE2, and PGD2) levels on days 7 and 21.. Interestingly, low doses of ivermectin cream (0.03–0.1%) induced wound healing with minimal scarring compared to higher doses of the cream and the positive control, Silver Sulfadiazine. Conclusion: Ivermectin promotes wound healing partly through modulation of the inflammatory process and the levels of Transforming Growth Factor-Beta 1 and Vascular Endothelial Growth Factor. Low doses of ivermectin cream have the potential to be used in treating wounds with minimal scar tissue formation. Keywords: Ivermectin, Hydroxyproline, TGF-β 1, VEGF, Cytokines, Growth factors, Eicosanoids
Background A wound is a break in the structural continuity regarding the morphology and the functionality of an organ [1]. Wound healing is, therefore, a progression of an intricate biochemical and physiological cascade that reestablishes the integral anatomy and functionality of the injured tissue [2]. Wound repair is a critical yet entangled process in mammals, with many different features represented by successive yet interwoven phases; hemostatic, inflammatory, proliferative, * Correspondence: [email protected] 1 Department of Pharmacology, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Full list of author information is available at the end of the article
and maturation phases [3]. Immediately after injury, the disrupted fibers activate platelet aggregation, resulting in degranulation and the release of clotting, chemotactic, and growth factors to initiate hemostasis [4]. Fibronectin, thrombin, and their derivatives from platelets inter
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