title: Therapeutic effect of dimethyl dimethoxy biphenyl dicarboxylate on collagen-induced arthritis in rats.
abstract: OBJECTIVE
  To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA).
  
  
  METHODS
  Wistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent.
  
  
  RESULTS
  Compared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.
  
  
  CONCLUSIONS
  Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.
authors.affiliation: Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, Menofia University, Sadat Branch, Sadat, 32897, Egypt. Robamtalaat@yahoo.com.
authors.forename: Roba M
authors.initials: RM
authors.lastname: Talaat
authors.affiliation: Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, Menofia University, Sadat Branch, Sadat, 32897, Egypt.
authors.forename: Amira S
authors.initials: AS
authors.lastname: Abo-El-Atta
authors.affiliation: Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, Menofia University, Sadat Branch, Sadat, 32897, Egypt.
authors.forename: Sabah M
authors.initials: SM
authors.lastname: Farou
authors.affiliation: Pathology Department, Faculty of Medicine, Tanta University, Tanta, 31111, Egypt.
authors.forename: Karima I
authors.initials: KI
authors.lastname: El-Dosoky
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003094:Collagen; D051546:Cyclooxygenase 2 / Q000097:blood; D004149:Dioxoles / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015847:Interleukin-4 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008727:Methotrexate / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D004149:Dioxoles; D016209:Interleukin-8; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4; D009569:Nitric Oxide; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; D003094:Collagen; D051546:Cyclooxygenase 2; D008727:Methotrexate
keywords: angiogenesis; collagen-induced arthritis; dimethyl dimethoxy biphenyl dicarboxylate; inflflammation; rheumatoid arthritis