Protective effects of ONO-5046·Na, a specific neutrophil elastase inhibitor, on postperfusion lung injury

Yamazaki, Takenori; Ooshima, Hideki; Usui, Akihiko; Watanabe, Takashi; Yasuura, K

doi:10.1016/s0003-4975(99)00831-0

Cited by 58 publications

(37 citation statements)

References 19 publications

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“…Several investigators administered sivelestat to attenuate lung injury associated with CPB in different animal models. 4,7,24) All showed that sivelestat reduced inflammation related to CPB and 3 reported protective effects on pulmonary functions. In a clinical setting, Abe, et al reported that patients administered sivelestat had a shorter hospital stay in comparison to the patients in the placebo group.…”

Section: Discussionmentioning

confidence: 99%

“…Sivelestat sodium hydrate, sodium N-{2-[4-(2,2-dimethylpropionyloxy) phyenylsulfonylamino] benzoyl} aminoacetate tetrahydrate (Elaspol, ONO-5046-Na [C 20 H 21 N 2 NaO 7 S-Na-4H 2 O, molecular weight, 528.51]; Ono Pharmaceutical, Osaka, Japan), is a synthetic, specific, low-molecular weight neutrophil elastase inhibitor. 4) This drug has been used clinically to treat acute lung injury associated with systemic inflammatory response syndrome. 5,6) Matsuzaki, et al reported that sivelestat reduced neutrophil elastase and IL-8 levels in a simulated extracorporeal circulation.…”

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confidence: 99%

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Neutrophil Elastase Inhibitor Sivelestat Attenuates Perioperative Inflammatory Response in Pediatric Heart Surgery With Cardiopulmonary Bypass

et al. 2013

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SummaryCardiopulmonary bypass (CPB) evokes activation of a systemic inflammatory response. Sivelestat has been used clinically to treat acute lung injury associated with systemic inflammatory response syndrome. This prospective, doubleblind, randomized study was designed to evaluate the effects of sivelestat in the perioperative period of elective pediatric open-heart surgery with CPB. Twenty-six consecutive pediatric patients weighing between 5 and 10 kg and undergoing open-heart surgery with CPB were divided into a sivelestat group (n = 13) and a control group (n = 13). The patients in the sivelestat group were administered a continuous intravenous infusion of 0.2 mg/kg/hour of sivelestat, and the patients in the control group were administered the same volume of 0.9% saline from the initiation of CPB to 24 hours after surgery. Blood samples were drawn for the measurement of cytokines, polymorphonuclear elastase (PMN-E), white blood cell count (WBC), neutrophil count (NC), and C-reactive protein (CRP). There were no significant differences in cytokine data between the two groups. The peak PMN-E and WBC levels were significantly increased in the control group (P = 0.049, P = 0.039). The WBC and NC levels immediately after surgery in the control group were significantly greater than those in the sivelestat group (P = 0.049, P = 0.044). The peak CRP level in the control group was significantly greater than the sivelestat group (P = 0.04), and the CRP level on postoperative day 4 in the control group was significantly greater than in the sivelestat group (P = 0.014). This study showed that sivelestat attenuates the perioperative inflammatory response in pediatric heart surgery with CPB. (Int Heart J 2013; 54: 149-153)

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Neutrophil Elastase Inhibitor Sivelestat Attenuates Perioperative Inflammatory Response in Pediatric Heart Surgery With Cardiopulmonary Bypass

et al. 2013

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“…Whether or not these effects of elastase facilitate or are required for neutrophil transmigration across the basement membrane (138,186,187), endothelium (155,(188)(189)(190), or epithelium (24,96,115) is controversial-although elastase is necessary for neutrophil migration into the lung in some circumstances (142,151,158,191) but not in others (192,193). Finally, in addition to its effects on epithelial permeability, elastase may also facilitate neutrophil transmigration by modulating de-adhesion from the epithelial surface (194,195).…”

Section: Neutrophil Elastasementioning

confidence: 99%

Transepithelial Migration of Neutrophils

Zemans¹,

Colgan²,

Downey³

2009

Am J Respir Cell Mol Biol

302

125

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“…The priority in renal transplantation, and the principal clinical goal of our research team, is the prevention of I/R injury and the reduction of ATN (1). Recent studies have suggested a significant relationship between I/R injury and neutrophils (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Neutrophils release various substances that cause tissue damage, including oxgen-free radicals, neutrophil elastase and arachidonic acid (9).…”

Section: Discussionmentioning

confidence: 99%

“…This inhibitor is clinically used to ameliorate acute respiratory distress syndrome. It is reported to have a positive effect on heart (5), lung (6)(7)(8), liver (9-11) and intestinal (12) I/R injury in experimental models; however, no study has addressed its effect on renal I/R injury.…”

Section: Introductionmentioning

confidence: 99%

The effect of neutrophil elastase inhibitor on acute tubular necrosis after renal ischemia-reperfusion injury

Matsuyama

Hayama²,

Funao³

et al. 2008

Mol Med Report

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Abstract. In renal transplantation, ischemia-reperfusion (I/R) injury is a major cause of renal dysfunction. Activated neutrophils are reported to be closely involved in I/R injury after renal transplantation. Neutrophil elastase, a protease released from activated neutrophils, damages tubular endothelial cells. We investigated the beneficial effect of neutrophil elastase inhibitor (ONO-5046.Na) on renal I/R injury in rats. The study was conducted using 10 male Lewis rats (270-320 g) that were intravenously administered ONO-5046.Na (30 mg/kg before ischemia and after reperfusion) (group A) and control rats (group B) in a 90-min renal warm I/R injury model. Neutrophil elastase expression was analyzed using immunohistochemical staining, and the degree of renal dysfunction was evaluated using H&E staining and blood biochemistry. Neutrophil elastase was detected in tubular endothelial cells. The necrotic area extended to and encompassed nearly all the ischemic kidney within 12 h after reperfusion. The necrotic area and the grade of neutrophil elastase staining were significantly reduced in group A compared to group B. Significant differences in blood urea nitrogen and serum creatinine levels were observed. Survival rates over a 14-day period were examined. No rats survived for more than 4 days in group B. However, 2 of the 10 rats (20%) in group A survived for a 14-day period. To conclude, ONO-5046.Na inhibits neutrophil elastase and reduces acute tubular necrosis. Thus, it is a potent therapeutic agent for the control of renal I/R injury in renal transplantation.

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Protective effects of ONO-5046·Na, a specific neutrophil elastase inhibitor, on postperfusion lung injury

Cited by 58 publications

References 19 publications

Neutrophil Elastase Inhibitor Sivelestat Attenuates Perioperative Inflammatory Response in Pediatric Heart Surgery With Cardiopulmonary Bypass

Neutrophil Elastase Inhibitor Sivelestat Attenuates Perioperative Inflammatory Response in Pediatric Heart Surgery With Cardiopulmonary Bypass

Transepithelial Migration of Neutrophils

The effect of neutrophil elastase inhibitor on acute tubular necrosis after renal ischemia-reperfusion injury

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