Sodium Valproate Improves Skin Flap Survival Via Gamma-Aminobutyric Acid and Histone Deacetylase Inhibitory System Publisher Pubmed



Ala M^{1, 2} ; Mohammad Jafari R¹ ; Nematian H^{1, 2} ; Ganjedanesh MR^{1, 2} ; Dehpour AR^{1, 2} Show Affiliations
Source: Journal of Surgical Research Published:2020

Abstract

Sodium valproate interacts with biological systems through different mechanisms such as activation of gamma-aminobutyric acid (GABA)-sensitive chloride channels and inhibition of histone deacetylase. In this study, we examined the effect of sodium valproate in random-pattern skin flap of rats and investigated its mechanisms of action. Different types of experiments were carried out. In acute treatment, different doses of sodium valproate (50, 100, 150, 300 mg/kg) were injected intraperitoneally 1 h before surgery. In chronic treatment, the substance was injected each day for 2 wk. The size of skin necrosis was measured 1 wk after the surgery. The rate of secondary healing, amount of weight gain, hair growth, and wound regeneration were measured 2 wk after operation. In acute treatment, sodium valproate (100 mg/kg) reduced significantly the length of skin necrosis (P < 0.05). Administration of bicuculline (competitive antagonist of GABAA, 20 mg/kg) increased the length of skin necrosis (P < 0.05). In addition, administration of 100 mg/kg of sodium valproate and subeffective dose of bicuculline (10 mg/kg) prevented the protective effect of sodium valproate on skin flap necrosis (P < 0.05). In the chronically treated skin flap group, 100 mg/kg of sodium valproate reduced the length of necrosis (P < 0.01). Weight gain in the valproate group was more than that in the control group (P < 0.05). Skin also healed faster in the sodium valproate group than in the control group (P < 0.001). Combination therapy of sodium valproate and trichostatin A (330 nmol/kg) reversed the effect of valproate (P < 0.05). This study demonstrate that sodium valproate accelerates skin secondary healing in a rat model of skin flap probably through a GABA and histone deacetylase–dependent mechanism. © 2019 Elsevier Inc.