Treatment sorafenib in the collagen-induced arthritis model

Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly targets the synovial tissue, cartilage and subchondral bone. Sorafenib is a multikinase inhibitor which used in hepatocellular, renal cell and thyroid cancer. The aim of this study is to present the potential therapeutic effects of sorafenib on experimental arthritis model. Fourty three Wistar albino female rats, aged 8-10 weeks were used. The rats were divided randomly into five groups. Group-I as control group (n=10), Group-II as arthritis group (n=7), Group-III as etanercept (5 mg/kg) group (n=8), Group-IV as high dose (30 mg/kg) sorafenib group (n=9) and Group-V as low dose (10 mg/kg) sorafenib group (n=9) were assigned. Arthritis in Group II, III, IV and V rats was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant (on 1st and 7th day). Sorafenib administration to Group IV and V was started after the onset of arthritis (14th day of study) with nasogastric cannula until the end of the study at the dose of 10 mg/kg to Group V and 30 mg/kg to the Group IV daily. Weekly the dose of 5 mg/kg etanercept was given to Group III subcutaneously. Trunk blood was collected from the rats that were sacrificed at the thirty third day and the hind legs of the rats were amputated below the knee for histopathological analysis. Vascular endothelial growth factor (VEGF), VEGFR2 (VEGF Receptor 2) and β-aktin (control) was evaluated by Western Blot method from the tissue homogenates. Perisynovial inflammation and cartilage-bone destruction in the paw were determined. When it has been matched the 33th day arthritis score of Group III, IV, V with 13th day arthritis score of its own groups and the 33th day arthritis score of Group II, was lower. According to the Group II, tissue VEGF and VEGFR2 levels of Group III, IV and V was lower. Significant decrease was seen on histopathological scoring, perisynovial inflamation and cartilage-bone desturiction score on the Group III, IV and V rats joint tissue samples when compared to Group II. This study is the first study which shows Sorafenib prevents cartilage-bone destruction on collagen induced artritis modal. The results preoccupied sorafenib which is an anti VEGF can be effective in romatoid arthritis treatment. Key words: Rheumatoid arthritis, sorafenib.