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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8621078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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