Folic Acid Promotes Wound Healing in Diabetic Mice by Suppression of Oxidative Stress

The aim of this study was to investigate the effects of folic acid on impaired wound healing in diabetic mice. Male mice were divided into three groups: group 1, the non-diabetic mice (control); group 2, the streptozotocin (STZ)-induced type 1 diabetic mice; and group 3, the diabetic mice that received a daily dose of 3 mg/kg folic acid via oral gavage. Full-thickness excision wounds were created with 8-mm skin biopsy punches. Each wound closure was continuously evaluated until the wound healed up. Wound healing was delayed in diabetic mice compared with the non-diabetic mice. There were significantly reduced levels of hydroxyproline content (indicator of collagen deposition) and glutathione in diabetic wounds, whereas levels of lipid peroxidation and protein nitrotyrosination were increased. Daily supplementation with folic acid restored diabetes-induced healing delay. Histopathology showed that folic acid supplementation accelerated granulation tissue formation, proliferation of fibroblasts, and tissue regeneration in diabetic mice. Interestingly, folic acid alleviated diabetes-induced impaired collagen deposition in wounds. Moreover, folic acid significantly decreased levels of lipid peroxidation, protein nitrotyrosination and glutathione depletion in diabetic wounds. In conclusion, our results indicate that folic acid supplementation may improve impaired wound healing via suppressing oxidative stress in diabetic mice.