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

Abstract

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 long-term 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.

Water-Soluble Components of Pinus pinaster Wood

“…A wide scope of applications has been suggested or pinosylvins including antifungal and antibacterial agents (Lindberg et al 2004;Lee et al 2005;Celimene et al 1999;Gref et al 2000;Venäläinen et al 2004) with activity towards Listeria monocytogenes (Gözü et al 2010), cytotoxicity against a murine hepatic carcinoma cell line (Välimaa et al 2007), antimetastatic activity (Park et al 2012), antiinflammatory action based on the reduction of blood reactive species (Jančinová et al 2012;Bauerova et al 2011), and angiogenic effects (Kimura and Sumiyoshi 2011).…”

A Novel Combination of Methotrexate and Epigallocatechin Attenuates the Overexpression of Pro-inflammatory Cartilage Cytokines and Modulates Antioxidant Status in Adjuvant Arthritic Rats

“…Excess generation of superoxide radical under oxidative stress causes increased dismutation of the radical into H 2 O 2 . Due to decreased level of catalase, H 2 O 2 have not been completely detoxified which leads to increased in lipid peroxidation [50]. Reduced glutathione is an intracellular thiol-rich tripeptide, which protects cell and tissue structure.…”

Selective inhibition of extracellular oxidants liberated from human neutrophils—A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine

“…Adjuvant arthritis was induced in male Lewis rats (160-180 g, Velaz, Prague, Czech Republic) by a single intradermal injection of heat-killed M. butyricum in incomplete Freund's adjuvant [24]. The study was performed in compliance with Principles of Laboratory Animal Care and was approved by the institutional Ethics Committee and by the State Veterinary and Food Administration of the Slovak Republic.…”