title: 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.
abstract: 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 (10mg/kg) alone and in combination with MTX (2mg/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 MTX and CoQ10. CoQ10 administration potentiated the antiarthritic effect of MTX. 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 MTX administration as evident by the regulation of oxidant/anti-oxidant balance and the inhibitory effects on TNF-α and IL-6 levels. These results revealed that CoQ10 can serve as a useful adjuvant and promote the safe use of MTX in the management of arthritis, not only by potentiating the antiarthritic effect of MTX, but also by alleviating MTX-induced hepatocellular injury.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. Electronic address: dmon_kamal@yahoo.com.
authors.forename: Mona K
authors.initials: MK
authors.lastname: Tawfik
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002478:Cells, Cultured; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000975:Antioxidants; D018501:Antirheumatic Agents; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014451:Ubiquinone; C024989:coenzyme Q10; D008727:Methotrexate
keywords: Coenzyme Q10; Freund's complete adjuvant; Hepatotoxicity; Methotreaxate; Rat