Ivermectin Increases Random-Pattern Skin Flap Survival in Rats: The Novel Role of GABAergic System

Ivermectin (IVM) was first used as an antiparasitic agent; however, the role of this drug evolved into a broad spectrum. Many mechanisms have been proposed, including interaction with the GABAergic system. Considering the presence of GABA receptor in the skin tissue and its role in ischemia-reperfus...

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Bibliographic Details
Published in:The Journal of surgical research 2021-03, Vol.259, p.431-441
Main Authors: Tabary, Mohammadreza, Aryannejad, Armin, Noroozi, Nafise, Tavangar, Seyed Mohammad, Mohammad Jafari, Razieh, Araghi, Farnaz, Dadkhahfar, Sahar, Dehpour, Ahmad Reza
Format: Article
Language:English
Subjects:
Animals
Baclofen - administration & dosage
Bicuculline - administration & dosage
Drug Repositioning
GABA a
GABA Antagonists - administration & dosage
GABA B
GABA-A Receptor Antagonists - administration & dosage
gamma-Aminobutyric Acid - metabolism
Graft Survival - drug effects
Humans
Ivermectin
Ivermectin - administration & dosage
Male
Models, Animal
Rat
Rats
Receptors, GABA-A - metabolism
Receptors, GABA-B - metabolism
Skin - drug effects
Skin - metabolism
Skin flap
Surgical Flaps - adverse effects
Surgical Flaps - transplantation
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Summary:Ivermectin (IVM) was first used as an antiparasitic agent; however, the role of this drug evolved into a broad spectrum. Many mechanisms have been proposed, including interaction with the GABAergic system. Considering the presence of GABA receptor in the skin tissue and its role in ischemia-reperfusion I/R injury, we aimed to evaluate the effect of IVM through GABA receptors on random-pattern skin flap survival. Sixty Wistar male rats were used. Multiple doses of IVM (0.01, 0.05, 0.2, and 0.5 mg/kg) were injected intraperitoneally before the surgery. Baclofen (selective GABAB agonist) and bicuculline (selective GABAA antagonist) were administered in combination with IVM to assess the role of the GABAergic system. Histopathological evaluations, immunohistochemical staining, quantitative assessment of IL-1β and TNFα, and the expression of GABAA α1 subunit and GABAB R1 receptors were evaluated in the skin tissue. IVM 0.05 mg/kg could significantly increase flap survival compared with the control group (P 
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2020.09.010