Combination of coenzyme Q10 with methotrexate suppresses Freund's complete adjuvant-induced synovial inflammation with reduced hepatotoxicity in rats: Effect on oxidative stress and inflammation

Methotrexate (MTX) is a cornerstone disease modifying anti-rheumatic drug. One of its major drawbacks is hepatotoxicity, resulting in poor compliance of therapy. Coenzyme Q10 (CoQ10) is an antioxidant and anti-inflammatory compound, possessing both anti-arthritic and hepatoprotective potential. The present study was carried out to evaluate the effect of CoQ10 (10 mg/kg) alone and in combination with MTX (2 mg/kg) on the progression of adjuvant-induced arthritis in rats, and to elucidate the potential properties of CoQ10 in ameliorating MTX-induced liver damage in rats. Rats were assigned to; normal, arthritic, MTX treated, CoQ10 treated or a combination of MIX and CoQ10. CoQ10 administration potentiated the antiarthritic effect of MIX. Moreover, the combination therapy was effective in attenuating the severity of MTX-induced liver damage displayed by the improvement in hepatospecific serum markers and confirmed by the histo-pathological evaluation. Additionally, it attenuated the hepatic oxidative stress and the intensity of inflammatory mediators associated with MIX administration as evident by the regulation of oxidant/anti-oxidant balance and the inhibitory effects on TNF-alpha and IL-6 levels. These results revealed that CoQ10 can serve as a useful adjuvant and promote the safe use of MIX in the management of arthritis, not only by potentiating the antiarthritic effect of MTX, but also by alleviating MIX-induced hepatocellular injury. (C) 2014 Elsevier B.V. All rights reserved.