scholarly journals Neutrophil Elastase Inhibitors Suppress Oxidative Stress in Lung during Liver Transplantation

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Weifeng Yao ◽  
Xue Han ◽  
Yu Guan ◽  
Jianqiang Guan ◽  
Shan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Transplantation ◽  
Neutrophil Elastase ◽  
Barrier Function ◽  
Neutrophil Infiltration ◽  
Polymorphonuclear Neutrophil ◽  
Myeloperoxidase Activity ◽  
Sivelestat Sodium Hydrate ◽  
Sodium Hydrate ◽  
Sivelestat Sodium

Background. Neutrophil infiltration plays a critical role in the pathogenesis of acute lung injury following liver transplantation (LT). Neutrophil elastase is released from neutrophils during pulmonary polymorphonuclear neutrophil activation and sequestration. The aim of the study was to investigate whether the inhibition of neutrophil elastase could lead to the restoration of pulmonary function following LT. Methods. In in vivo experiments, lung tissue and bronchoalveolar lavage fluid (BALF) were collected at 2, 4, 8, and 24 h after rats were subjected to orthotopic autologous LT (OALT), and neutrophil infiltration was detected. Next, neutrophil elastase inhibitors, sivelestat sodium hydrate (exogenous) and serpin family B member 1 (SERPINB1) (endogenous), were administered to rats before OALT, and neutrophil infiltration, pulmonary oxidative stress, and barrier function were measured at 8 h after OALT. Results. Obvious neutrophil infiltration occurred from 2 h and peaked at 8 h in the lungs of rats after they were subjected to OALT, as evidenced by an increase in naphthol-positive cells, BALF neutrophil elastase activity, and lung myeloperoxidase activity. Treatment with neutrophil elastase inhibitors, either sivelestat sodium hydrate or SERPINB1, effectively reduced lung naphthol-positive cells and BALF inflammatory cell content, increased expression of lung HO-1 and tight junction proteins ZO-1 and occludin, and increased the activity of superoxide dismutase. Conclusion. Neutrophil elastase inhibitors, sivelestat sodium hydrate and SERPINB1, both reduced lung neutrophil infiltration and pulmonary oxidative stress and finally restored pulmonary barrier function.

scholarly journals Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase

2013 ◽  
Vol 7 (4) ◽  
pp. 1091-1095 ◽  
Author(s):  
NOBUHIKO YOSHIKAWA ◽  
TAISUKE INOMATA ◽  
YOSHIKATSU OKADA ◽  
TAIJU SHIMBO ◽  
MASATSUGU TAKAHASHI ◽  
...  
Keyword(s):  
Lung Injury ◽  
Neutrophil Elastase ◽  
Sivelestat Sodium Hydrate ◽  
Sodium Hydrate ◽  
Radiation Induced ◽  
Sivelestat Sodium

EFFECTS OF SPECIFIC NEUTROPHIL ELASTASE INHIBITOR, SIVELESTAT SODIUM HYDRATE, IN MURINE MODEL OF SEVERE PNEUMOCOCCAL PNEUMONIA

2007 ◽  
Vol 33 (2) ◽  
pp. 71-80 ◽  
Author(s):  
Katsunori Yanagihara ◽  
Yuichi Fukuda ◽  
Masafumi Seki ◽  
Koichi Izumikawa ◽  
Yoshitsugu Miyazaki ◽  
...  
Keyword(s):  
Murine Model ◽  
Neutrophil Elastase ◽  
Pneumococcal Pneumonia ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor ◽  
Sivelestat Sodium Hydrate ◽  
Sodium Hydrate ◽  
Sivelestat Sodium

scholarly journals Huangkui Capsule Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Macrophage Activation by Suppressing Inflammation and Oxidative Stress in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jinfang Deng ◽  
Zhenpeng He ◽  
Xiuru Li ◽  
Wei Chen ◽  
Ziwen Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Macrophage Activation ◽  
Neutrophil Infiltration ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Myeloperoxidase Activity ◽  
Tnf Α ◽  
And Oxidative Stress

Background. Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of Abelmoschus manihot (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. Methods. Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance. Results. LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically attenuated the lung wet/dry weight ratio, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24 h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF-α and IL-6 in RAW 264.7 cells. Conclusions. These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.

Abstract 122: Sivelestat Sodium Hydrate Treatment for Patients with Kawasaki Disease refractory to initial intravenous immunoglobulin therapy

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Ryota Ebata ◽  
Kumi Yasukawa ◽  
Yuko Saito ◽  
Kouji Higashi ◽  
Nobuyuki Takada ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Laboratory Data ◽  
Total Duration ◽  
Ivig Therapy ◽  
University Hospital ◽  
Intravenous Immunoglobulin Therapy ◽  
Sivelestat Sodium Hydrate ◽  
Significant Difference ◽  
Sodium Hydrate ◽  
Sivelestat Sodium

Background: There are still no definite treatments for refractory Kawasaki disease (KD). In this pilot study, we evaluated the safety and efficacy of a new protocol consisting of sivelestat sodium hydrate (SSH) combined with additional intravenous immune globulin (IVIG) for KD patients who were resistant to initial IVIG therapy. Methods: We prospectively collected clinical data of KD patients who were resistant to initial IVIG (2g/kg for one day) and received SSH (0.2mg/kg/hour for consecutive 5 days) combined with additional IVIG (2g/kg for one day) as a second-line therapy at Chiba University hospital between December 2006 and March 2014. We defined patients who remained febrile (37.5°C or more of an axillary temperature) after 36 to 48 hours after start of initial IVIG therapy or who had recrudescent fever associated with other symptoms of Kawasaki disease as being resistant to initial IVIG. Results: Thirty five KD patients were enrolled in this study. No serious adverse effect was noted. The median total duration of fever was 8 days (range 6 to 17 days) and the incidence of coronary artery lesion (CAL) was 5.7% (2 of 35 patients). Among a total of 35 patients, 24 (69%) of them responded promptly to be afebrile 36 to 48 hours after the start of the additional IVIG with SSH. One of these 24 patients developed CAL. The other 11 (31%) failed to become afebrile 36 to 48 hours after the start of the additional IVIG with SSH therapy. Of these 11 patients, one developed CAL. Before initial IVIG, there was no difference in demographic and laboratory data except the age, body weight and % Neutrophils. However, after initial IVIG therapy, there appeared significant difference in % Neutrophils and C-reactive protein levels and both of which were higher in additional IVIG with SSH therapy non-responders than in responders. Conclusions: Additional IVIG combined with SSH for the additional treatment of KD patients who were refractory to initial IVIG therapy was safe and the incidence of CAL is acceptable considering the severity of patients in this study.

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