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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.
Pulm Pharmacol Ther. 2010 Oct; 23(5):425-31.PP

Abstract

Cysteinyl-leukotrienes (cysLTs) and thromboxane A(2) (TXA(2)) are important mediators in inflammatory lung diseases such as bronchial asthma and idiopathic pulmonary fibrosis (IPF). We examined the effects of inhaled KP-496, a novel dual antagonist of the cysLTs and TXA(2) receptors, on bleomycin-induced IPF in mice. Mice were intravenously injected bleomycin on day 0, and 0.5% of KP-496 was inhaled twice a day (30 min/time) for the entire experimental period. The effects of KP-496 were evaluated by the number of infiltrated cells in bronchoalveolar lavage fluid (BALF), hydroxyl-L-proline content in the lung, and histopathology. Analyses of BALF on days 7 and 21 revealed that inhaled KP-496 significantly decreased total cell numbers, macrophages, neutrophils, and eosinophils on both days. KP-496 significantly decreased hydroxyl-L-proline content in the lung on day 21. Histopathological analyses of lungs on day 21 demonstrated that KP-496 significantly suppressed inflammatory and fibrotic changes. Our results suggested that the suppression of cysLTs and TXA(2) pathways by KP-496 could control airway inflammation and pulmonary fibrosis, and that KP-496 could be a new therapeutic agent for lung diseases with inflammation and fibrogenesis such as IPF and chronic obstructive pulmonary disease.

Authors+Show Affiliations

Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Yamashina-ku, Kyoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20457270

Citation

Kurokawa, Shigeo, et al. "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." Pulmonary Pharmacology & Therapeutics, vol. 23, no. 5, 2010, pp. 425-31.
Kurokawa S, Suda M, Okuda T, et al. 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. Pulm Pharmacol Ther. 2010;23(5):425-31.
Kurokawa, S., Suda, M., Okuda, T., Miyake, Y., Matsumura, Y., Ishimura, M., Saito, R., & Nakamura, T. (2010). 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. Pulmonary Pharmacology & Therapeutics, 23(5), 425-31. https://doi.org/10.1016/j.pupt.2010.04.008
Kurokawa S, et al. 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. Pulm Pharmacol Ther. 2010;23(5):425-31. PubMed PMID: 20457270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kurokawa,Shigeo, AU - Suda,Masahiro, AU - Okuda,Toshiaki, AU - Miyake,Yoshihide, AU - Matsumura,Yuzuru, AU - Ishimura,Masakazu, AU - Saito,Ryota, AU - Nakamura,Tsutomu, Y1 - 2010/05/10/ PY - 2009/07/08/received PY - 2010/04/06/revised PY - 2010/04/30/accepted PY - 2010/5/12/entrez PY - 2010/5/12/pubmed PY - 2010/12/14/medline SP - 425 EP - 31 JF - Pulmonary pharmacology & therapeutics JO - Pulm Pharmacol Ther VL - 23 IS - 5 N2 - Cysteinyl-leukotrienes (cysLTs) and thromboxane A(2) (TXA(2)) are important mediators in inflammatory lung diseases such as bronchial asthma and idiopathic pulmonary fibrosis (IPF). We examined the effects of inhaled KP-496, a novel dual antagonist of the cysLTs and TXA(2) receptors, on bleomycin-induced IPF in mice. Mice were intravenously injected bleomycin on day 0, and 0.5% of KP-496 was inhaled twice a day (30 min/time) for the entire experimental period. The effects of KP-496 were evaluated by the number of infiltrated cells in bronchoalveolar lavage fluid (BALF), hydroxyl-L-proline content in the lung, and histopathology. Analyses of BALF on days 7 and 21 revealed that inhaled KP-496 significantly decreased total cell numbers, macrophages, neutrophils, and eosinophils on both days. KP-496 significantly decreased hydroxyl-L-proline content in the lung on day 21. Histopathological analyses of lungs on day 21 demonstrated that KP-496 significantly suppressed inflammatory and fibrotic changes. Our results suggested that the suppression of cysLTs and TXA(2) pathways by KP-496 could control airway inflammation and pulmonary fibrosis, and that KP-496 could be a new therapeutic agent for lung diseases with inflammation and fibrogenesis such as IPF and chronic obstructive pulmonary disease. SN - 1522-9629 UR - https://www.unboundmedicine.com/medline/citation/20457270/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1094-5539(10)00053-2 DB - PRIME DP - Unbound Medicine ER -