Mechanisms of ivermectin-induced wound healing

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 be...

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Main Authors: Daniel Kwesi Sia, Kwesi Boadu Mensah, Tony Opoku-Agyemang, Raphael D. Folitse, David Obiri Darko
Format: Article
Language:English
Published: BMC 2020-10-01
Series:BMC Veterinary Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12917-020-02612-z
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author Daniel Kwesi Sia
Kwesi Boadu Mensah
Tony Opoku-Agyemang
Raphael D. Folitse
David Obiri Darko
author_facet Daniel Kwesi Sia
Kwesi Boadu Mensah
Tony Opoku-Agyemang
Raphael D. Folitse
David Obiri Darko
author_sort Daniel Kwesi Sia
collection DOAJ
description 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.
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spelling doaj.art-e6c9d9a276e5464ca8a743e5067f621a2022-12-22T01:16:44ZengBMCBMC Veterinary Research1746-61482020-10-0116111210.1186/s12917-020-02612-zMechanisms of ivermectin-induced wound healingDaniel Kwesi Sia0Kwesi Boadu Mensah1Tony Opoku-Agyemang2Raphael D. Folitse3David Obiri Darko4Department of Pharmacology, College of Health Sciences, Kwame Nkrumah University of Science and TechnologyDepartment of Pharmacology, College of Health Sciences, Kwame Nkrumah University of Science and TechnologySchool of Veterinary Medicine, College of Health Sciences, Kwame Nkrumah University of Science and TechnologySchool of Veterinary Medicine, College of Health Sciences, Kwame Nkrumah University of Science and TechnologyDepartment of Pharmacology, College of Health Sciences, Kwame Nkrumah University of Science and TechnologyAbstract 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.http://link.springer.com/article/10.1186/s12917-020-02612-zIvermectinHydroxyprolineTGF-β 1VEGFCytokinesGrowth factors
spellingShingle Daniel Kwesi Sia
Kwesi Boadu Mensah
Tony Opoku-Agyemang
Raphael D. Folitse
David Obiri Darko
Mechanisms of ivermectin-induced wound healing
BMC Veterinary Research
Ivermectin
Hydroxyproline
TGF-β 1
VEGF
Cytokines
Growth factors
title Mechanisms of ivermectin-induced wound healing
title_full Mechanisms of ivermectin-induced wound healing
title_fullStr Mechanisms of ivermectin-induced wound healing
title_full_unstemmed Mechanisms of ivermectin-induced wound healing
title_short Mechanisms of ivermectin-induced wound healing
title_sort mechanisms of ivermectin induced wound healing
topic Ivermectin
Hydroxyproline
TGF-β 1
VEGF
Cytokines
Growth factors
url http://link.springer.com/article/10.1186/s12917-020-02612-z
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