Batroxobin Promotes Wound Healing after Burn Injury by Enhancing Blood Flow

BACKGROUND: In the process of burn wound healing, promoting healing and suppressing wound progression by enhancing blood flow is considered essential. Various agents that increase blood flow are currently being assessed. Batroxobin (DF-521; Defibrase) is a defibrinogenating agent extracted from Bothrops moojeni , used as a thrombin-like serine protease to improve ischemic conditions. However, it remains unclear how this agent affects the burn wound healing process. In this study, the authors conducted analyses to define the effects of batroxobin administration on burn wound healing. METHODS: Full-thickness burn wounds were created on the dorsal skin of C57BL/6 mice by applying a 90°C, 5-mm-diameter soldering iron for 10 seconds. Immediately after wounding, batroxobin (30 batroxobin units/kg per mouse) was administered intraperitoneally daily. As a vehicle control, the same volume of saline was administered. The authors analyzed wound area, histologic findings, blood flow, growth factor and chemokine synthesis, and factor expression related to ischemia-reperfusion. RESULTS: The authors found that the systemic administration of batroxobin prevented burn wound progression, which was accompanied by decreased expression of tumor necrosis factor-α and NOX2 and reduced synthesis of hypoxia-inducible factor-1α. In addition, this agent promoted wound healing by enhancing blood flow, increasing S100A4 + fibroblast accumulation, and stimulating the production of growth factors (basic fibroblast growth factor, epidermal growth factor, and placental growth factor). CONCLUSIONS: These results indicate that the systemic administration of batroxobin prevented burn wound progression and accelerated the healing process by enhancing blood flow. CLINICAL RELEVANCE STATEMENT: The authors demonstrated that the treatment of batroxobin accelerated angiogenesis and S100A4-positive fibroblast accumulation, accompanied by increased local basic fibroblast growth factor production. In addition, batroxobin was found to reduce burn wound progression.