Chymase as a Novel Therapeutic Target in Acute Pancreatitis

Acute pancreatitis is still a life-threatening disease without an evidenced therapeutic agent. In this study, the effect of chymase in acute pancreatitis and the possible effect of a chymase inhibitor in acute pancreatitis were investigated. Hamsters were subcutaneously administered 3.0 g/kg of L-ar...

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Autores principales:	Toru Kuramoto, Denan Jin, Koji Komeda, Kohei Taniguchi, Fumitoshi Hirokawa, Shinji Takai, Kazuhisa Uchiyama
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	acute pancreatitis chymase inhibitor inflammation survival rate hamster Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2206a3bb6bdf424882b881f48b906ad2
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id	oai:doaj.org-article:2206a3bb6bdf424882b881f48b906ad2
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spelling	oai:doaj.org-article:2206a3bb6bdf424882b881f48b906ad22021-11-25T17:55:19ZChymase as a Novel Therapeutic Target in Acute Pancreatitis10.3390/ijms2222123131422-00671661-6596https://doaj.org/article/2206a3bb6bdf424882b881f48b906ad22021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12313https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Acute pancreatitis is still a life-threatening disease without an evidenced therapeutic agent. In this study, the effect of chymase in acute pancreatitis and the possible effect of a chymase inhibitor in acute pancreatitis were investigated. Hamsters were subcutaneously administered 3.0 g/kg of L-arginine to induce acute pancreatitis. Biological markers were measured 1, 2, and 8 h after L-arginine administration. To investigate the effect of a chymase inhibitor, a placebo (saline) or a chymase inhibitor TY-51469 (30 mg/kg) was given 1 h after L-arginine administration. The survival rates were evaluated for 24 h after L-arginine administration. Significant increases in serum lipase levels and pancreatic neutrophil numbers were observed at 1 and 2 h after L-arginine administration, respectively. Significant increases in pancreatic neutrophil numbers were observed in the placebo-treated group, but they were significantly reduced in the TY-51469-treated group. A significant increase in the pancreatic tumor necrosis factor-α mRNA level was observed in the placebo-treated group, but it disappeared in the TY-51469-treated group. Chymase activity significantly increased in the placebo-treated group, but it was significantly reduced by treatment with TY-51469. The survival rate significantly improved in the TY-51469-treated group. A chymase inhibitor may become a novel therapeutic agent for acute pancreatitis.Toru KuramotoDenan JinKoji KomedaKohei TaniguchiFumitoshi HirokawaShinji TakaiKazuhisa UchiyamaMDPI AGarticleacute pancreatitischymaseinhibitorinflammationsurvival ratehamsterBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12313, p 12313 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute pancreatitis chymase inhibitor inflammation survival rate hamster Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	acute pancreatitis chymase inhibitor inflammation survival rate hamster Biology (General) QH301-705.5 Chemistry QD1-999 Toru Kuramoto Denan Jin Koji Komeda Kohei Taniguchi Fumitoshi Hirokawa Shinji Takai Kazuhisa Uchiyama Chymase as a Novel Therapeutic Target in Acute Pancreatitis
description	Acute pancreatitis is still a life-threatening disease without an evidenced therapeutic agent. In this study, the effect of chymase in acute pancreatitis and the possible effect of a chymase inhibitor in acute pancreatitis were investigated. Hamsters were subcutaneously administered 3.0 g/kg of L-arginine to induce acute pancreatitis. Biological markers were measured 1, 2, and 8 h after L-arginine administration. To investigate the effect of a chymase inhibitor, a placebo (saline) or a chymase inhibitor TY-51469 (30 mg/kg) was given 1 h after L-arginine administration. The survival rates were evaluated for 24 h after L-arginine administration. Significant increases in serum lipase levels and pancreatic neutrophil numbers were observed at 1 and 2 h after L-arginine administration, respectively. Significant increases in pancreatic neutrophil numbers were observed in the placebo-treated group, but they were significantly reduced in the TY-51469-treated group. A significant increase in the pancreatic tumor necrosis factor-α mRNA level was observed in the placebo-treated group, but it disappeared in the TY-51469-treated group. Chymase activity significantly increased in the placebo-treated group, but it was significantly reduced by treatment with TY-51469. The survival rate significantly improved in the TY-51469-treated group. A chymase inhibitor may become a novel therapeutic agent for acute pancreatitis.
format	article
author	Toru Kuramoto Denan Jin Koji Komeda Kohei Taniguchi Fumitoshi Hirokawa Shinji Takai Kazuhisa Uchiyama
author_facet	Toru Kuramoto Denan Jin Koji Komeda Kohei Taniguchi Fumitoshi Hirokawa Shinji Takai Kazuhisa Uchiyama
author_sort	Toru Kuramoto
title	Chymase as a Novel Therapeutic Target in Acute Pancreatitis
title_short	Chymase as a Novel Therapeutic Target in Acute Pancreatitis
title_full	Chymase as a Novel Therapeutic Target in Acute Pancreatitis
title_fullStr	Chymase as a Novel Therapeutic Target in Acute Pancreatitis
title_full_unstemmed	Chymase as a Novel Therapeutic Target in Acute Pancreatitis
title_sort	chymase as a novel therapeutic target in acute pancreatitis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2206a3bb6bdf424882b881f48b906ad2
work_keys_str_mv	AT torukuramoto chymaseasanoveltherapeutictargetinacutepancreatitis AT denanjin chymaseasanoveltherapeutictargetinacutepancreatitis AT kojikomeda chymaseasanoveltherapeutictargetinacutepancreatitis AT koheitaniguchi chymaseasanoveltherapeutictargetinacutepancreatitis AT fumitoshihirokawa chymaseasanoveltherapeutictargetinacutepancreatitis AT shinjitakai chymaseasanoveltherapeutictargetinacutepancreatitis AT kazuhisauchiyama chymaseasanoveltherapeutictargetinacutepancreatitis
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Chymase as a Novel Therapeutic Target in Acute Pancreatitis

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