Effect of inhaled KP-496, a novel dual antagonist of the cysteinyl leukotriene and thromboxane A2 receptors, on a bleomycin-induced pulmonary fibrosis model in mice

Kurokawa, Shigeo; Suda, Masashi; Okuda, Toshiaki; Miyake, Yoshihide; Matsumura, Yuzuru; Ishimura, Masakazu; Saito, Ryota; Nakamura, Tsutomu

doi:10.1016/j.pupt.2010.04.008

Cited by 9 publications

(5 citation statements)

References 50 publications

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“…Similarly, a novel dual antagonist of the cyst LT and thromboxane A2 receptors significantly decreased cell numbers in BALF on a bleomycin-induced pulmonary fibrosis model in mice on day seven and 21. [28] Consistent with lung tissue MPO activity, in which an enzyme is predominantly found in the azurophilic granules of polymorphonuclear leukocytes, increased following bleomycin administration, this increase was effectively reversed by montelukast, concomitantly with BALF neutrophil accumulation. Similarly, Izumo et al [29] reported decreased number of inflammatory cells in BALF of montelukast treated mice on seventh day.…”

Section: Discussionmentioning

confidence: 69%

Protective effect of cysteinyl leukotriene receptor antagonist montelukast in bleomycin-induced pulmonary fibrosis

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et al. 2018

Turk Gogus Kalp Dama

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Bu çalışmada bir hayvan modelinde bleomisin ile indüklenmiş enflamatuvar ve oksidatif akciğer hasarında montelukast kullanılarak sistenil lökotrien aktivitesinin farmakolojik inhibisyonunun erken ve geç dönem etkileri araştırıldı. Ça lış ma pla nı: Çalışmaya 48 erkek Wistar albino sıçan (ağırlık 250 g-300 g) dahil edildi. Sıçanlara intratrakeal bleomisin veya serum fizyolojik uygulandı ve sıçanlar montelukast veya serum fizyolojik alacak şekilde gruplara ayrıldı. Bleomisin uygulamasından dört ve 15 gün sonra bronkoalveolar lavaj sıvısı ve akciğer doku örnekleri alındı. Bul gu lar: Bleomisin tümör nekroz faktör-alfa düzeylerinde (kontrollerde 4.0±1.4 pg/mL'ye karşı erken dönemde 44.1±14.5 pg/mL, geç dönemde 30.3±5.7 pg/mL, sırasıyla, p<0.001 ve p<0.001), transforme edici büyüme faktörü-beta 1 düzeylerinde (28.6±6.6 pg/mL'ye karşı erken dönemde 82.3±14.1 pg/mL, geç dönemde 60.1±2.9 pg/mL, sırasıyla, p<0.001 ve p<0.001) ve fibrozis skorunda (erken dönemde 1.85±0.89'a karşı geç dönemde 5.60±1.14, sırasıyla, p<0.001 ve p<0.01) anlamlı artışlara yol açtı. Bleomisine maruz kalan sıçanlarda kolajen içeriği sadece geç dönemde arttı (kontrollerde 15.3±3.0 μg/mg'a karşı geç dönemde 29.6±9.1 μg/mg, p<0.001]. Montelukast tedavisi tüm bu biyokimyasal işaretlerle beraber bleomisinin indüklediği histopatolojik alterasyonları tersine çevirdi. So nuç: Montelukast, bleomisin ile indüklenmiş enflamatuvar ve oksidatif akciğer hasarını hafifletmekte ve kolajen depolanmasını ve fibrotik yanıtı azaltmaktadır. Dolayısıyla, sistenil lökotrien reseptör antagonistleri idyopatik pulmoner fibrozis için yeni teröpatik ajanlar olarak dikkate alınabilir. Anah tar söz cük ler: Bleomisin; kolajen; glutatyon; interstisyel akciğer hastalığı; malondialdehit; miyeloperoksidaz; transforme edici büyüme faktörü-beta 1; tümör nekroz faktör-alfa.

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Section: Discussionmentioning

confidence: 69%

Protective effect of cysteinyl leukotriene receptor antagonist montelukast in bleomycin-induced pulmonary fibrosis

Topaloğlu

Yıldızeli

Şener

et al. 2018

Turk Gogus Kalp Dama

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“…Due to the profibrotic effect of TXA2, various TP receptor antagonists have been used in antifibrosis research. For example, KP-496 and NTP42, TP antagonists that suppress acute or chronic lung inflammation and pulmonary fibrosis by inhibiting mast cell recruitment and pulmonary collagen deposition, may be expected to be new therapeutic agents for lung diseases characterized by inflammation and fibrogenesis, such as IPF and chronic obstructive pulmonary disease [ 103 , 104 ]. Moreover, the selective TP antagonist terutroban significantly prevents both TGF-1β and HSP47 expression, both of which play an important role in the onset and progression of various fibrotic diseases, to inhibit collagen deposition in the aortic wall of salt-loaded spontaneously hypertensive stroke-prone rats (SHRSPs) [ 105 ].…”

Section: Prostaglandinsmentioning

confidence: 99%

The Roles of Various Prostaglandins in Fibrosis: A Review

Zhao

Wang

et al. 2021

Biomolecules

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Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular matrix and eventually leads to the destruction of the tissue structure and impaired organ function. Prostaglandins are produced by arachidonic acid through cyclooxygenases and various prostaglandin-specific synthases. Prostaglandins bind to homologous receptors on adjacent tissue cells in an autocrine or paracrine manner and participate in the regulation of a series of physiological or pathological processes, including fibrosis. This review summarizes the properties, synthesis, and degradation of various prostaglandins, as well as the roles of these prostaglandins and their receptors in fibrosis in multiple models to reveal the clinical significance of prostaglandins and their receptors in the treatment of fibrosis.

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“…In addition, CCK8 experiments were performed, and it was found that LTD4 reduced the activity of type II ACE cells, which could be reversed by administration of baicalin. CysLTs/TP dual antagonists could inhibit nonacute pulmonary inflammation and also inhibit pulmonary fibrosis [35].…”

Section: Discussionmentioning

confidence: 99%

Baicalin Ameliorates Radiation-Induced Lung Injury by Inhibiting the CysLTs/CysLT1 Signaling Pathway

Bao

Wang

Zhu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Radiation-induced lung injury (RILI) is a common complication of radiotherapy for thoracic tumors. This study investigated the alleviating effect of baicalin (BA) on RILI and its possible mechanism. Methods. RILI model was established by chest irradiation (IR) of C57BL/6 mice for 16 weeks. Different concentrations of BA were administered, and dexamethasone (DXM) was used as a positive control. Then, the lung pathological changes were observed by HE and Masson staining. The levels of TGF-β, TNF-α, IL-1β, IL-6, CysLT, LTC4, and LTE4 were measured by ELISA. The CysLT1 expression was detected by qPCR, immunohistochemistry, and western blot. Type II AEC cells were pretreated with LTD-4 to establish the RILI cell model and intervened with different concentrations of BA. Then, the collagen I protein level was measured by ELISA. The CysLT1 and α-SMA expression were detected by qPCR, immunofluorescence, and western blot. Results. BA could effectively improve lung histopathological changes and pulmonary fibrosis. In vivo, BA could inhibit the levels of TGF-β, TNF-α, IL-1β, and IL-6 and reduce the levels of CysLT, LTC4, and LTE4. In vitro, different concentrations of LTD4 could reduce the viability of type II AEC cells, which could be reversed by the administration of different concentrations of BA. In addition, BA could reduce CysLT1 mRNA, as well as CysLT1 and α-SMA protein levels in vitro and in vivo. Conclusion. BA attenuated lung inflammation and pulmonary fibrosis by inhibiting the CysLTs/CysLT1 pathway, thereby protecting against RILI.

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Effect of inhaled KP-496, a novel dual antagonist of the cysteinyl leukotriene and thromboxane A2 receptors, on a bleomycin-induced pulmonary fibrosis model in mice

Cited by 9 publications

References 50 publications

Protective effect of cysteinyl leukotriene receptor antagonist montelukast in bleomycin-induced pulmonary fibrosis

Protective effect of cysteinyl leukotriene receptor antagonist montelukast in bleomycin-induced pulmonary fibrosis

The Roles of Various Prostaglandins in Fibrosis: A Review

Baicalin Ameliorates Radiation-Induced Lung Injury by Inhibiting the CysLTs/CysLT1 Signaling Pathway

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