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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: Kuramoto, Toru, Jin, Denan, Komeda, Koji, Taniguchi, Kohei, Hirokawa, Fumitoshi, Takai, Shinji, Uchiyama, Kazuhisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621078/
https://www.ncbi.nlm.nih.gov/pubmed/34830195
http://dx.doi.org/10.3390/ijms222212313
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author Kuramoto, Toru
Jin, Denan
Komeda, Koji
Taniguchi, Kohei
Hirokawa, Fumitoshi
Takai, Shinji
Uchiyama, Kazuhisa
author_facet Kuramoto, Toru
Jin, Denan
Komeda, Koji
Taniguchi, Kohei
Hirokawa, Fumitoshi
Takai, Shinji
Uchiyama, Kazuhisa
author_sort Kuramoto, Toru
collection PubMed
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.
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spelling pubmed-86210782021-11-27 Chymase as a Novel Therapeutic Target in Acute Pancreatitis Kuramoto, Toru Jin, Denan Komeda, Koji Taniguchi, Kohei Hirokawa, Fumitoshi Takai, Shinji Uchiyama, Kazuhisa Int J Mol Sci Article 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. MDPI 2021-11-15 /pmc/articles/PMC8621078/ /pubmed/34830195 http://dx.doi.org/10.3390/ijms222212313 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kuramoto, Toru
Jin, Denan
Komeda, Koji
Taniguchi, Kohei
Hirokawa, Fumitoshi
Takai, Shinji
Uchiyama, Kazuhisa
Chymase as a Novel Therapeutic Target in Acute Pancreatitis
title 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_short Chymase as a Novel Therapeutic Target in Acute Pancreatitis
title_sort chymase as a novel therapeutic target in acute pancreatitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621078/
https://www.ncbi.nlm.nih.gov/pubmed/34830195
http://dx.doi.org/10.3390/ijms222212313
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