Description
Sivelestat is an inhibitor of neutrophil elastase that exhibits cardioprotective, anti-inflammatory, and anticancer activities. In vitro, sivelestat decreases superoxide dismutase (SOD) adduct formation and in vivo, it decreases SOD levels, resulting in a decrease in myocardial infarction size and improvement in left ventricular contractility. In other cellular models, sivelestat decreases induction of iNOS and production of NO and also prevents activation of NF-κB and expression of the IL-1 receptor. Sivelestat inhibits contraction of tracheal and bronchial rings, decreasing airway hyperresponsiveness. Additionally, this compound inhibits release of TGF-α, PDGF-AA, PDGF-BB, and VEGF in esophageal carcinoma cells, inhibiting cell invasion and proliferation.
References
Aune SE, Yeh ST, Kuppusamy P, et al. Sivelestat attenuates myocardial reperfusion injury during brief low flow postischemic infusion. Oxid Med Cell Longev. 2013;2013:279847. PMID: 23766850.
Araki Y, Matsumiya M, Matsuura T, et al. Sivelestat suppresses iNOS gene expression in proinflammatory cytokine-stimulated hepatocytes. Dig Dis Sci. 2011 Jun;56(6):1672-81. PMID: 21221803.
Wada Y, Yoshida K, Tsutani Y, et al. Neutrophil elastase induces cell proliferation and migration by the release of TGF-alpha, PDGF and VEGF in esophageal cell lines. Oncol Rep. 2007 Jan;17(1):161-7. PMID: 17143494.
Takayama N, Uchida K. Epithelium-dependent and -independent inhibitory effects of sivelestat, a neutrophil elastase inhibitor, on substance P-induced contraction of airway smooth muscle in lipopolysaccharide-treated guinea-pigs. J Smooth Muscle Res. 2005 Oct;41(5):257-70. PMID: 16428865.
