The effects of valproic acid on skin healing: experimental study in rats

PURPOSE: To recognize the effects of valproic acid (VPA), an epigenetic drug, on the skin healing process. METHODS: Sixty male Wistar rats were divided into two groups: the experiment treated with VPA (100 mg/kg/day); and the control, with 0.9% sodium chloride by gavage. Skin healing was studied in three moments (the third, the seventh, and the 14th day), evaluating the parameters: inflammatory reaction and its intensity (anti-LCA), angiogenesis (anti-CD34), collagen I and III (anti-collagen I, anti-collagen III and Picrosirius-red F3BA) and myofibroblasts (anti-alpha-AMS). RESULTS: The inflammatory reaction was acute or sub-acute in both groups on the third day. On the seventh and the 14th day, chronic predominated in the control (p=0.006), and sub-acute in the experiment (p=0.020). There was a greater number of leukocytes in the group treated only on the third day (p=0.036). The number of vessels was lower in the treated group at the three times (p3=0.002, p7<0.001, and p14=0.027). Myofibroblasts were rare in the third day and moderate quantity in the remaining periods. Collagen I density was higher in the control at the three times (p<0.001) and collagen III in the treated group (p<0.001). CONCLUSIONS: VPA led to a more intense inflammatory reaction, decreased angiogenesis and collagen deposition, especially type I collagen.