Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jakubowski, A; Maksimovich, N; Olszanecki, R; Gebska, A; Gasser, H; Podesser, BK; Hallstrom, S; Chlopicki, S.
S-nitroso human serum albumin given after LPS challenge reduces acute lung injury and prolongs survival in a rat model of endotoxemia.
NAUNYN-SCHMIED ARCH PHARMACOL. 2009; 379(3): 281-290.
Doi: 10.1007/s00210-008-0351-2
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Hallström Seth
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- Abstract:
- Endotoxemia leads to the induction of inducible nitric oxide synthase (NOS-2) and increased expression of numerous inflammatory mediators contributing to endotoxin-induced acute lung injury. We tested the hypothesis that supplementation of nitric oxide (NO) by the novel NO donor S-nitroso human serum albumin (S-NO-HSA) given after lipopolysaccharide (LPS) challenge may reduce NOS-2 expression, lung inflammation and acute lung injury. Rats were divided into four groups: sham-operated (no treatment), LPS, LPS+HSA (human serum albumin), and LPS+S-NO-HSA. LPS was administered intravenously (20 mg kg(-1)) resulting in acute lung injury and a high mortality rate within 6 h (>90%). LPS-induced lung injury was characterized by an increased lung edema (lung wet/dry weight ratio), pulmonary neutrophil infiltration (myeloperoxidase activity, MPO) as well as a robust inflammatory response [increased expression of intercellular adhesion molecule-1 (ICAM-1), NOS-2, and cyclooxygenase-2 (COX-2)]. Infusion of S-NO-HSA or HSA was started 2 h after LPS and continued for 4 h (total dose of 72 mg kg(-1)) at a rate of 300 microg kg(-1) min(-1). S-NO-HSA but not HSA prolonged survival of endotoxemic rats, reduced the hypotensive response to LPS, minimized LPS-induced lung edema and injury, normalized MPO activity as well as diminished lung expression of pro-inflammatory molecules such as ICAM-1, NOS-2, and COX-2. Continuous supplementation of NO by S-NO-HSA after LPS challenge prevents induction of NOS-2, provides significant protection of endotoxin-induced acute lung injury, and prevents early mortality in endotoxic shock in rats. Our results suggest a potential therapeutic role for S-NO-HSA in endotoxemia.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Blood Pressure - drug effects
- Cyclooxygenase 2 - biosynthesis
- Disease Models, Animal -
- Drug Administration Schedule -
- Endotoxemia - complications
- Humans -
- Intercellular Adhesion Molecule-1 - biosynthesis
- Kaplan-Meier Estimate -
- Lipopolysaccharides -
- Lung - drug effects
- Nitric Oxide Synthase Type II - biosynthesis
- Nitroso Compounds - administration and dosage
- Peroxidase - metabolism
- Pulmonary Edema - etiology
- Rats -
- Rats, Wistar -
- Serum Albumin - administration and dosage
- Find related publications in this database (Keywords)
- Nitric oxide
- S-nitroso human serum albumin
- Acute lung injury
- Endotoxemia
- Rats