OBJECTIVE AND DESIGN: The present study aimed to investigate the combined effects of a neutrophil elastase inhibitor, sivelestat sodium, with a free radical scavenger, edaravone, on lipolysaccharide (LPS)-induced acute lung injury (ALI). MATERIALS AND METHODS: Adult male Sprague-Dawley rats were anesthetized and instilled intratracheally with 2 mg/kg LPS. Sivelestat sodium (10 mg/kg, i.p.) and/or edaravone (8 mg/kg, i.p.) were administered 1 h after LPS instillation. The severity of pulmonary injuries was evaluated 12 h after inducing acute lung injury. RESULTS: In lung tissues, either sivelestat or edaravone treatment alone showed significant protective effects against neutrophil infiltration and tissue injury, as demonstrated by myeloperoxidase activity and histopathological analysis. Sivelestat or edaravone treatment also attenuated the LPS-induced production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in rat lungs. However, the LPS-induced elevation of malondialdehyde levels in rat lungs was reduced only by edaravone, but not by sivelestat. In addition, combined treatment with both sivelestat and edaravone demonstrated additive protective effects on LPS-induced lung injury, compared with single treatments. CONCLUSIONS: Combination of sivelestat and edaravone shows promise as a new treatment option for ALI/acute respiratory distress syndrome patients.
OBJECTIVE AND DESIGN: The present study aimed to investigate the combined effects of a neutrophil elastase inhibitor, sivelestat sodium, with a free radical scavenger, edaravone, on lipolysaccharide (LPS)-induced acute lung injury (ALI). MATERIALS AND METHODS: Adult male Sprague-Dawley rats were anesthetized and instilled intratracheally with 2 mg/kg LPS. Sivelestat sodium (10 mg/kg, i.p.) and/or edaravone (8 mg/kg, i.p.) were administered 1 h after LPS instillation. The severity of pulmonary injuries was evaluated 12 h after inducing acute lung injury. RESULTS: In lung tissues, either sivelestat or edaravone treatment alone showed significant protective effects against neutrophil infiltration and tissue injury, as demonstrated by myeloperoxidase activity and histopathological analysis. Sivelestat or edaravone treatment also attenuated the LPS-induced production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in rat lungs. However, the LPS-induced elevation of malondialdehyde levels in rat lungs was reduced only by edaravone, but not by sivelestat. In addition, combined treatment with both sivelestat and edaravone demonstrated additive protective effects on LPS-induced lung injury, compared with single treatments. CONCLUSIONS: Combination of sivelestat and edaravone shows promise as a new treatment option for ALI/acute respiratory distress syndromepatients.
Authors: Gordon D Rubenfeld; Ellen Caldwell; Eve Peabody; Jim Weaver; Diane P Martin; Margaret Neff; Eric J Stern; Leonard D Hudson Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245