title: Combined methotrexate and coenzyme Q₁₀ therapy in adjuvant-induced arthritis evaluated using parameters of inflammation and oxidative stress.
abstract: Rheumatoid arthritis is a common severe joint disease that affects all age groups, it is thus of great importance to develop new strategies for its treatment. The aim of the present study was to examine the combined effect of coenzyme Q₁₀ (CoQ₁₀) and methotrexate (MTX) on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritis (AA) was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experiments included healthy animals, arthritic animals not treated, arthritic animals treated with CoQ₁₀, with methotrexate, and with a combination of CoQ₁₀ and methotrexate. The two latter groups received a daily oral dose of 20 mg/kg b.w. of CoQ₁₀, either alone or with methotrexate in an oral dose of 0.3 mg/kg b.w. twice a week. We found that CoQ₁₀ potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect of methotrexate on the level of oxidation of proteins (suppression of protein carbonyl level in plasma) as well as lipoperoxidation (suppression of levels of HNE-adducts and MDA-adducts to plasma proteins). The same effect was observed for plasmatic levels of CoQ₉ and IL-1α, and partially also for γ-glutamyltransferase activity assessed in joints and spleen. Moreover, the combination therapy improved the functionality of peripheral blood neutrophils in AA, with a balancing effect on the immunosuppression caused by MTX monotherapy. In summary, combined administration of CoQ₁₀ and methotrexate suppressed arthritic progression in rats more effectively than did MTX alone. This finding may help improve treatment of rheumatoid arthritis.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. katarina.bauerova@savba.sk
authors.forename: Katarina
authors.initials: K
authors.lastname: Bauerova
authors.forename: Ema
authors.initials: E
authors.lastname: Paulovicova
authors.forename: Danica
authors.initials: D
authors.lastname: Mihalova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Drafi
authors.forename: Miriam
authors.initials: M
authors.lastname: Strosova
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mascia
authors.forename: Fiorella
authors.initials: F
authors.lastname: Biasi
authors.forename: Jozef
authors.initials: J
authors.lastname: Rovensky
authors.forename: Jarmila
authors.initials: J
authors.lastname: Kucharska
authors.forename: Anna
authors.initials: A
authors.lastname: Gvozdjakova
authors.forename: Silvester
authors.initials: S
authors.lastname: Ponist
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D014451:Ubiquinone / Q000627:therapeutic use*
chemical_list: D053582:Interleukin-1alpha; D014451:Ubiquinone; C030571:ubiquinone 9; D008727:Methotrexate