title: Markers of inflammation and oxidative stress studied in adjuvant-induced arthritis in the rat on systemic and local level affected by pinosylvin and methotrexate and their combination.
abstract: Oxidative stress (OS) is important in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and its experimental model--adjuvant arthritis (AA). Antioxidants are scarcely studied in autoimmunity, and future analyses are needed to assess its effects in ameliorating these diseases. Although there are studies about antioxidants effects on the course of RA, their role in combination therapy has not yet been studied in detail, especially on extra-articular manifestations of AA. During the 28-d administration of pinosylvin (PIN) in monotherapy and in combination with methotrexate (MTX) to AA rats, we evaluated the impact of the treatment on selected parameters. The experiment included: healthy controls, untreated AA, AA administered 50 mg/kg b.w. of PIN daily p.o., AA administered 0.4 mg/kg b.w. of MTX twice weekly p.o. and AA treated with a combination of PIN+MTX. AA was monitored using: hind paw volume, C-reactive protein, monocyte chemotactic protein-1 (MCP-1), thiobarbituric acid reactive substances (TBARS) and F2-isoprostanes in plasma, γ-glutamyltransferase activity in spleen, activity of lipoxygenase (LOX) in lung, heme oxygenase-1 (HO-1) and nuclear factor kappa B (NF-κB) in liver and lung. PIN monotherapy significantly improved the activation of NF-κB in liver and lung, HO-1 expression and activity of LOX in the lung, MCP-1 levels in plasma (on 14th d) and plasmatic levels of F2-isoprostanes. An important contribution of PIN to MTX effect was the reduction of OS (an increase of HO-1 expression in lung and reduction of plasmatic TBARS) and decrease of LOX activity in the lung.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences , Bratislava , Slovak Republic .
authors.forename: Katarina
authors.initials: K
authors.lastname: Bauerova
authors.forename: Alessandra
authors.initials: A
authors.lastname: Acquaviva
authors.forename: Silvester
authors.initials: S
authors.lastname: Ponist
authors.forename: Concetta
authors.initials: C
authors.lastname: Gardi
authors.forename: Daniela
authors.initials: D
authors.lastname: Vecchio
authors.forename: Frantisek
authors.initials: F
authors.lastname: Drafi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arezzini
authors.forename: Lydia
authors.initials: L
authors.lastname: Bezakova
authors.forename: Viera
authors.initials: V
authors.lastname: Kuncirova
authors.forename: Danica
authors.initials: D
authors.lastname: Mihalova
authors.forename: Radomir
authors.initials: R
authors.lastname: Nosal
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D028441:F2-Isoprostanes / Q000097:blood; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006614:Hindlimb; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008084:Lipoxygenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism; D000094162:Phytoalexins
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D018932:Chemokine CCL2; D028441:F2-Isoprostanes; D051547:Heme Oxygenase-1; D008084:Lipoxygenase; D008727:Methotrexate; D016328:NF-kappa B; D013267:Stilbenes; D017392:Thiobarbituric Acid Reactive Substances; D005723:gamma-Glutamyltransferase; C491766:Ccl2 protein, rat; C049032:pinosylvin; D000094162:Phytoalexins
keywords: Autoimmunity; antioxidants; combination therapy; extra-articular manifestation; rheumatoid arthritis