The Mechanisms of the Anti-Inflammatory and Anti-Apoptotic Effects of Omega-3 Polyunsaturated Fatty Acids during Methotrexate-Induced Intestinal Damage in Cell Line and in a Rat Model.

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  • Additional Information
    • Source:
      Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI Publishing
    • Subject Terms:
      Anti-Inflammatory Agents/*administration & dosage ; Apoptosis/*drug effects ; Cytokines/*metabolism ; Fatty Acids, Omega-3/*administration & dosage ; Intestinal Mucosa/*cytology ; Methotrexate/*toxicity ; Mucositis/*therapy; Animals ; Anti-Inflammatory Agents/pharmacology ; Cell Proliferation ; Cell Survival/drug effects ; Cyclooxygenase 2/metabolism ; Enterocytes/cytology ; Enterocytes/drug effects ; Fatty Acids, Omega-3/pharmacology ; HCT116 Cells ; HT29 Cells ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Male ; Mucositis/chemically induced ; Mucositis/metabolism ; Mucositis/pathology ; NF-kappa B/metabolism ; Rats ; Rats, Sprague-Dawley
    • Abstract:
      Background: The aim of this study was to examine the anti-inflammatory and anti-apoptotic patterns of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during methotrexate (MTX) induced intestinal damage in cell culture and in a rat model. Methods: Non-treated and treated with MTX HT 29 and HCT116cells were exposed to increasing doses of n-3 PUFAs and cell viability was evaluated using PrestoBlue ® assay. Male Sprague-Dawley rats were divided into 4 experimental groups: Control rats, CONTR+n-3 PUFA rats that were treated with oral n-3 PUFA, MTX rats were treated with MTX given IP, and MTX+n-3 PUFA rats were treated with oral n-3 PUFA before and following injection of MTX. Intestinal mucosal parameters and mucosal inflammation, enterocyte proliferation and apoptosis, TNF-α in mucosal tissue and plasma (ELISA), NF-κB, COX-2, TNF-α, Fas, FasL, Fadd, Bid, Bax and Bcl-2gene and protein levels were determined 72 h following MTX injection. Results: Exposure of HT 29 and HCT116cells to n-3 PUFA attenuated inhibiting effects of MTX on cell viability. MTX-n-3 PUFA rats demonstrated a lower intestinal injury score and enhanced intestinal repair. A significant decrease in enterocyte apoptosis in MTX+n-3 PUFA rats was accompanied by decreased TNF-α, FAS, FasL, FADD and BID mRNA levels. Decreased NF-κB, COX-2 and TNF-α levels in mucosa was accompanied by a decreased number of IELs and macrophages. Conclusions: n-3 PUFAs inhibit NF-κB/COX-2 induced production of pro-inflammatory cytokines and inhibit cell apoptosis mainly by extrinsic pathway in rats with MTX-induced intestinal damage.
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    • Contributed Indexing:
      Keywords: COX-2; NF-κB; TNF-α; apoptosis; chemotherapy; intestine; mucositis
    • Accession Number:
      0 (Anti-Inflammatory Agents)
      0 (Cytokines)
      0 (Fatty Acids, Omega-3)
      0 (NF-kappa B)
      EC 1.14.99.- (Ptgs2 protein, mouse)
      EC 1.14.99.1 (Cyclooxygenase 2)
      YL5FZ2Y5U1 (Methotrexate)
    • Publication Date:
      Date Created: 20210403 Date Completed: 20210513 Latest Revision: 20210513
    • Publication Date:
      20240829
    • Accession Number:
      PMC8000946
    • Accession Number:
      10.3390/nu13030888
    • Accession Number:
      33801889