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.