Alginate oligosaccharide improves 5-fluorouracil-induced intestinal mucositis by enhancing intestinal barrier and modulating intestinal levels of butyrate and isovalerate.
Int J Biol Macromol
; 276(Pt 1): 133699, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38972652
ABSTRACT
Chemotherapy-induced mucositis (CIM) is the typical side effect of chemotherapy. This study investigates the potential of alginate oligosaccharide (AOS) in ameliorating CIM induced by 5-fluorouracil (5-FU) in a murine model and its underlying mechanisms. AOS effectively mitigated body weight loss and histopathological damage, modulated inflammatory cytokines and attenuated the oxidative stress. AOS restored intestinal barrier integrity through enhancing expression of tight junction proteins via MLCK signaling pathway. AOS alleviated intestinal mucosal damage by inhibiting TLR4/MyD88/NF-κB signaling pathway, downregulating the pro-apoptotic protein Bax and upregulating the anti-apoptotic protein Bcl-2. Moreover, AOS significantly enriched intestinal Akkermansiaceae and increased the production of short-chain fatty acids (SCFAs), most notably butyrate and isovalerate. Pre-treatment with butyrate and isovalerate also alleviated 5-FU-induced CIM. In conclusion, AOS effectively mitigated CIM through strenghthening intestinal barrier, attenuating inflammation, and modulating gut microbiota and intestianl levels of butyrate and isovalerate. These finding indicate that AOS could be potentially utilized as a supplemental strategy for prevention or mitigation of CIM.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligosaccharides
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Butyrates
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Alginates
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Mucositis
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Fluorouracil
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Intestinal Mucosa
Limits:
Animals
Language:
En
Journal:
Int J Biol Macromol
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: