Treatment pemertrexed in the collagen-induced arthritis model

Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly targets the synovial tissue, cartilage and subchondral bone. Pemetrexed (PMTX) is an antifolate drug, such as methotrexate. This study aimed to determine the effectiveness of PMTX that is a multitargeted antifolate on the collagen-induced arthritis (CIA) model.Fourty Wistar albino female rats, aged 8-10 weeks were used. The rats were randomized into four groups (n=10 in each group). Group-I as control group, Group-II as arthritis group, Group-III as low dose PMTX group and Group-IV as high dose PMTX group were assigned. Arthritis in Group-II, -III and -IV rats was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant. At the second and eighth day of arthritis development after the onset of arthritis, Group-III and group-IV rats were given intraperitoneal doses of 0.2 mg/kg and 1mg/kg PMTX, respectively.Trunk blood was collected from the rats that were sacrificed at the twenty ninth day and the hind legs of the rats were amputated below the knee for histopathological analysis. Serum tumor necrosis factor-alpha (TNF-?), interleukin (IL) -17, malondialdehide (MDA) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxides (GPx) activities, perisynovial inflammation and cartilage-bone destruction in the paw were determined.When compared with Group I rats, in the Group-II rats serum TNF-?, IL-17 and MDA levels were increased and SOD, CAT, GPx activities were decreased. Histopathological analysis demonstrated that extensive perisynovial inflammation, marked cartilage-bone destruction in Group-II rat. PMTX treatment decreased levels of TNF-?, IL-17, MDA and increased activities of SOD, CAT and GPx; it suppressed the perisynovial inflammation and prevented the cartilage-bone destruction.This study is the first to show that PMTX prevents the development of cartilage-bone destruction in the CIA model. These results suggest that PMTX might be a novel Disease Modifying Antirheumatic Drug (DMARD) for the treatment of rheumatoid arthritis.Key words: Rheumatoid arthritis, collagen induced arthritis, pemetrexed.