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Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin
BACKGROUND: Indomethacin is one of the group of nonsteroidal anti-inflammatory drugs, which often cause gastric mucosal injury as a side effect. Infiltration and activation of inflammatory cells, production of proinflammatory cytokines and chemokines, generation of reactive oxygen species, and activ...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Japan
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443347/ https://www.ncbi.nlm.nih.gov/pubmed/22402774 http://dx.doi.org/10.1007/s00535-012-0564-5 |
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author | Nakajima, Atsushi Fukui, Toshiro Takahashi, Yu Kishimoto, Masanobu Yamashina, Masao Nakayama, Shinji Sakaguchi, Yutaku Yoshida, Katsunori Uchida, Kazushige Nishio, Akiyoshi Yodoi, Junji Okazaki, Kazuichi |
author_facet | Nakajima, Atsushi Fukui, Toshiro Takahashi, Yu Kishimoto, Masanobu Yamashina, Masao Nakayama, Shinji Sakaguchi, Yutaku Yoshida, Katsunori Uchida, Kazushige Nishio, Akiyoshi Yodoi, Junji Okazaki, Kazuichi |
author_sort | Nakajima, Atsushi |
collection | PubMed |
description | BACKGROUND: Indomethacin is one of the group of nonsteroidal anti-inflammatory drugs, which often cause gastric mucosal injury as a side effect. Infiltration and activation of inflammatory cells, production of proinflammatory cytokines and chemokines, generation of reactive oxygen species, and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric injury. We examined whether sake yeast-derived thioredoxin (a small redox-active protein with anti-oxidative activity and various redox-regulating functions) reduced indomethacin-induced gastric injury. METHODS: Gastric injury was produced by the intraperitoneal administration of indomethacin (40 mg/kg body weight) to C57BL/6 mice. Prior to the administration of indomethacin, the mice were offered food pellets containing non-genetically modified sake yeast-derived thioredoxin (thioredoxin 200 μg/g) for 3 days. Histological examinations, assessment of myeloperoxidase activity, and analysis of the gene expressions of proinflammatory cytokines and a chemokine (interleukin [IL]-1β, IL-6, and CXCL1) were statistically evaluated. Indomethacin cytotoxicity was determined by lactate dehydrogenase release from murine gastric epithelial GSM06 cells induced by 24-h treatment with 200 and 400 μM indomethacin after 1-h preincubation with 100 μg/ml sake yeast-derived thioredoxin. RESULTS: Macroscopic (edema, hemorrhage, and ulcers) and histological (necrosis, submucosal edema, neutrophil infiltration) findings induced by indomethacin were significantly reduced by pretreatment with food pellets containing thioredoxin. Gastric myeloperoxidase activity and the gene expressions of proinflammatory cytokines (IL-1β and IL-6) were also significantly reduced by this pretreatment compared with findings in the mice not pretreated with thioredoxin-containing food pellets. The administration of sake yeast-derived thioredoxin significantly reduced indomethacin-induced cytotoxicity in GSM06 cells. CONCLUSIONS: We conclude that oral administration of sake yeast-derived thioredoxin reduces indomethacin-induced gastric injury. Sake yeast-derived thioredoxin may have therapeutic potential against indomethacin-induced gastric injury. |
format | Online Article Text |
id | pubmed-3443347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer Japan |
record_format | MEDLINE/PubMed |
spelling | pubmed-34433472012-09-20 Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin Nakajima, Atsushi Fukui, Toshiro Takahashi, Yu Kishimoto, Masanobu Yamashina, Masao Nakayama, Shinji Sakaguchi, Yutaku Yoshida, Katsunori Uchida, Kazushige Nishio, Akiyoshi Yodoi, Junji Okazaki, Kazuichi J Gastroenterol Original Article—Alimentary Tract BACKGROUND: Indomethacin is one of the group of nonsteroidal anti-inflammatory drugs, which often cause gastric mucosal injury as a side effect. Infiltration and activation of inflammatory cells, production of proinflammatory cytokines and chemokines, generation of reactive oxygen species, and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric injury. We examined whether sake yeast-derived thioredoxin (a small redox-active protein with anti-oxidative activity and various redox-regulating functions) reduced indomethacin-induced gastric injury. METHODS: Gastric injury was produced by the intraperitoneal administration of indomethacin (40 mg/kg body weight) to C57BL/6 mice. Prior to the administration of indomethacin, the mice were offered food pellets containing non-genetically modified sake yeast-derived thioredoxin (thioredoxin 200 μg/g) for 3 days. Histological examinations, assessment of myeloperoxidase activity, and analysis of the gene expressions of proinflammatory cytokines and a chemokine (interleukin [IL]-1β, IL-6, and CXCL1) were statistically evaluated. Indomethacin cytotoxicity was determined by lactate dehydrogenase release from murine gastric epithelial GSM06 cells induced by 24-h treatment with 200 and 400 μM indomethacin after 1-h preincubation with 100 μg/ml sake yeast-derived thioredoxin. RESULTS: Macroscopic (edema, hemorrhage, and ulcers) and histological (necrosis, submucosal edema, neutrophil infiltration) findings induced by indomethacin were significantly reduced by pretreatment with food pellets containing thioredoxin. Gastric myeloperoxidase activity and the gene expressions of proinflammatory cytokines (IL-1β and IL-6) were also significantly reduced by this pretreatment compared with findings in the mice not pretreated with thioredoxin-containing food pellets. The administration of sake yeast-derived thioredoxin significantly reduced indomethacin-induced cytotoxicity in GSM06 cells. CONCLUSIONS: We conclude that oral administration of sake yeast-derived thioredoxin reduces indomethacin-induced gastric injury. Sake yeast-derived thioredoxin may have therapeutic potential against indomethacin-induced gastric injury. Springer Japan 2012-03-09 2012 /pmc/articles/PMC3443347/ /pubmed/22402774 http://dx.doi.org/10.1007/s00535-012-0564-5 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article—Alimentary Tract Nakajima, Atsushi Fukui, Toshiro Takahashi, Yu Kishimoto, Masanobu Yamashina, Masao Nakayama, Shinji Sakaguchi, Yutaku Yoshida, Katsunori Uchida, Kazushige Nishio, Akiyoshi Yodoi, Junji Okazaki, Kazuichi Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin |
title | Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin |
title_full | Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin |
title_fullStr | Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin |
title_full_unstemmed | Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin |
title_short | Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin |
title_sort | attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin |
topic | Original Article—Alimentary Tract |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443347/ https://www.ncbi.nlm.nih.gov/pubmed/22402774 http://dx.doi.org/10.1007/s00535-012-0564-5 |
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