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N‐feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis
Author(s) -
Kuncirova Viera,
Ponist Silvester,
Mihalova Danica,
Drafi Frantisek,
Nosal Radomir,
Acquaviva Alessandra,
Gardi Concetta,
Harmatha Juraj,
Hradkova Iveta,
Bauerova Katarina
Publication year - 2014
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12085
Subject(s) - methotrexate , medicine , arthritis , inflammation , rheumatoid arthritis , adjuvant , adjuvant therapy , pharmacology , oncology , chemotherapy
Many of disease‐modifying anti‐rheumatic drugs often have side effects at high doses and/or during long‐term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis ( RA ). The aim of the study was to examine the effect of N‐feruloylserotonin (N‐f‐5 HT ) and methotrexate ( MTX ) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund′s adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N‐f‐5 HT in the oral daily dose of 15 mg/kg b.w., arthritic animals with administration of MTX in the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with the combination of N‐f‐5 HT and MTX . N‐f‐5 HT in monotherapy reduced only activation of NF ‐κB and did not have any significant effect on other parameters monitored. Low‐dose treatment of MTX decreased the level of IL ‐1β and MCP ‐1 on day 14 and activation of NF ‐κB in liver without significant effect on other parameters. N‐f‐5 HT and MTX combination showed both the anti‐arthritic (hind paw volume and arthritic score) and anti‐inflammatory effect (plasmatic levels of IL ‐1β, IL ‐17, MCP ‐1, CRP , and activation of NF ‐κB in liver). In combination with MTX , N‐f‐5 HT markedly potentiated the therapeutic effect of MTX low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of RA .