Inositol-1,2,6-trisphosphate in the treatment of burns

Abstract

Burns are often associated with severe pain, complicated wound healing and disfiguring and functionally limiting scar formation. The vast inflammatory response of the burn wound may produce local and systemic complications resulting in fluid imbalance and impaired immune defense complicated by infections, altered metabolism and organ dysfunction. The inflammatory response is also involved in the pathophysiology of progressive ischemia that may follow thermal injury. It has been postulated that limiting the inflammatory reaction of a burn injury could reduce the risk of tissue loss as well as local and systemic complications. Recently, D-myo-inositol-1,2,6-trisphosphate (1,2,6-IP3), an isomer of the intracellular messenger inositol-1,4,5-trisphosphate, was shown to possess anti-inflammatory properties. The aim of this study was to evaluate the influence of 1,2,6-IP3 on the pathophysiology of experimental burns, and reveal possible therapeutical implications.A 1 cm2 standardized full-thickness experimental burn was produced in the abdominal skin of anesthetized rats. Burned animals received 1,2,6-IP3 as intravenous infusions or as a topically applied cream. Albumin extravasation, blood flow or eicosanoid formation in the burned skin or muscle were analyzed. Evans blue was used as a marker of albumin extravasation and quantified spectrophotometrically or by digital image color analysis. Postburn blood flow was measured by laser Doppler flowmetry. The synthesis and release of the inflammatory mediators prostaglandin E, thromboxane B2 and leukotriene B4 was analyzed by RIA ex vivo.Results showed that 1,2,6-IP3 significantly inhibited progressive ischemia and burn-induced edema, measured both by invasive and non-invasive techniques. 1,2,6-IP3 also significantly reduced the formation of thromboxane B2 and leukotriene B4 in burned skin. In conclusion, the present thesis present original results showing beneficial effects by 1,2,6-IP3 on burn pathophysiology possibly mediated by the anti-inflammatory properties of the agent.