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Interdisciplinary Toxicology

The Journal of Institute of Experimental Pharmacology of Slovak Academy of Sciences

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Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress

Katarína Bauerová1 / Silvester Poništ1 / Danica Mihalová1 / František Dráfi1 / Viera Kuncírová1

Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, SK-84104 Bratislava, Slovak Republic1

This content is open access.

Citation Information: Interdisciplinary Toxicology. Volume 4, Issue 1, Pages 33–39, ISSN (Online) 1337-9569, ISSN (Print) 1337-6853, DOI: 10.2478/v10102-011-0007-9, April 2011

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Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress

As a number 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 safety of longterm therapy of RA is very important as patients with RA are usually treated for two or more decades. This experimental overview is focused on some promising substances and their combinations with the standard antirheumatic drug - methotrexate (Mtx) for treatment of rheumatoid arthritis. The adjuvant arthritis model in Lewis rats was used for evaluation of antiinflammatory efficacy of the substances evaluated. Mtx was administered in the oral dose of 0.3 mg/kg b.w. twice a week. Natural and synthetic antioxidants were administered in the daily oral dose of 20 mg/kg b.w for coenzyme Q10 (CoQ10), 150 mg/kg b.w for carnosine (Carn), 15 mg/kg b.w. for stobadine dipalmitate (Stb) and its derivative SMe1.2HCl (SMe1), and 30 mg/kg b.w. for pinosylvin (Pin) or pterostilbene (Pte). Mtx in the oral dose of 0.4 mg/kg b.w. twice a week was combined with Pin in the oral daily dose of 50 mg/kg b.w. Clinical (hind paw volume - HPV), biochemical (activity of GGT in joint and level of TBARS in plasma), and immunological (IL-1 in plasma) parameters were assessed. Our results achieved with different antioxidants in monotherapies showed a reduction of oxidative stress in adjuvant arthritis independently of the chemical structure of the compounds. Pin was the most effective antioxidant tested in decreasing HPV. All combinations tested showed a higher efficacy in affecting biochemical or immunological parameters than Mtx administered in monotherapy. The findings showed the benefit of antioxidant compounds for their use in combination therapy with methotrexate.

Keywords: arthritis; methotrexate; combination therapy; oxidative stress; carnosine; coenzyme Q10; pyridoindoles; stilbenoids

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