Abstract |
Inflammatory bowel diseases (IBD) are chronic and relapsing gastrointestinal disorders, where a significant proportion of patients are unresponsive or lose response to traditional and currently used therapies. In the current study, we propose a new concept for anti-inflammatory treatment based on a selective acidic mammalian chitinase (AMCase) inhibitor. The functions of chitinases remain unclear, but they have been shown to be implicated in the pathology of various inflammatory disorders regarding the lung ( asthma, idiopathic pulmonary fibrosis) and gastrointestinal tract (IBD and colon cancer). The aim of the study is to investigate the impact of AMCase inhibitor (OAT-177) on the dextran sulfate sodium (DSS)-induced models of colitis. In the short-term therapeutic protocol, OAT-177 given intragastrically in a 30 mg/kg dose, twice daily, produced a significant (p < 0.001) anti-inflammatory effect, as shown by the macroscopic score. Additionally, OAT-177 significantly decreased TNF-α mRNA levels and MPO activity compared to DSS-only treated mice. Intraperitoneal administration of OAT-177 at a dose of 50 mg/kg caused statistically relevant reduction of the colon length. In the long-term therapeutic protocol, OAT-177 given intragastrically in a dose of 30 mg/kg, twice daily, significantly improved colon length and body weight compared to DSS-induced colitis. This is the first study proving that AMCase inhibitors may have therapeutic potential in the treatment of IBD.
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Authors | Marzena Mazur, Jakub Włodarczyk, Mikołaj Świerczyński, Radzisław Kordek, Marcin M Grzybowski, Jacek Olczak, Jakub Fichna |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 23
Issue 4
(Feb 15 2022)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 35216274
(Publication Type: Journal Article)
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Chemical References |
- Anti-Inflammatory Agents
- Cytokines
- Dextran Sulfate
- Chitinases
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Chitinases
(antagonists & inhibitors)
- Colitis
(chemically induced, drug therapy, metabolism)
- Colon
(drug effects, metabolism)
- Cytokines
(metabolism)
- Dextran Sulfate
(pharmacology)
- Disease Models, Animal
- Female
- Inflammatory Bowel Diseases
(chemically induced, drug therapy, metabolism)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
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