S-nitroso-human-albumin A new therapeutic approach in endotoxic shock

INTRODUCTION Endotoxemia leads to induction of inducible nitric oxide synthase (iNOS) and increased expression of numerous inflammatory mediators, contributing to endotoxin-induced acute lung injury. OBJECTIVES We examined the hypothesis that supplementation of nitric oxide (NO) with the novel NO donor, S-nitroso-human-serum-albumin (S-NO-HSA), may reduce iNOS expression, lung inflammation and acute lung injury in a rat model of septic shock. MATERIAL AND METHODS Rats were divided into 4 groups: sham-operated (no treatment), LPS (lipopolysaccharide), LPS + HSA, and LPS + S-NO-HSA. Endotoxin-induced (20 mg kg(-1), iv) lung injury was characterized by measurement of wet/dry weight ratio (pulmonary edema), myeloperoxidase activity (pulmonary neutrophil infiltration), expression of intercellular adhesion molecule-1, iNOS, and cyclooxygenase-2. RESULTS LPS-induced acute lung injury involved pulmonary edema, neutrophil infiltration and a strong inflammatory response, resulting in high mortality within 6 h. S-NO-HSA prolonged survival of endotoxemic rats, reduced hypotensive response to LPS, and minimized LPS-induced lung edema by modulation of systemic inflammatory response. CONCLUSIONS NO supplementation with S-NO-HSA after LPS administration prevents induction of iNOS, protects against endotoxin-induced acute lung injury, and reduces early mortality in endotoxic rats. The results of the study support a therapeutic role of S-NO-HSA in the treatment of endotoxemia.