S-nitroso-human-albumin: a new therapeutic approach in endotoxic shock.
BACKGROUND
Endotoxemia leads to induction of inducible nitric oxide synthase (iNOS) and increased expression of numerous inflammatory mediators, contributing to endotoxin-induced acute lung injury.


OBJECTIVE
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.


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.
Jakubowski
Andrzej
A
Institute of Experimental Pharmacology, Jagiellonian University School of Medicine, Kraków, Poland. mfjakubo@cyf-kr.edu.pl
D000818:Animals; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects; D009603:Nitroso Compounds / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000517:prevention & control* / Q000821:virology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000627:therapeutic use*; D000075462:Serum Albumin, Human
D016207:Cytokines; D008070:Lipopolysaccharides; D009603:Nitroso Compounds; C511514:S-nitrosoalbumin, human; D012709:Serum Albumin; D000075462:Serum Albumin, Human