Lapatınıb treatment ın the collagen-ınduced arthrıtıs model

The purpose of this study was to investigate the therapeutic effect of lapatinib on collagen-induced arthritis (CIA) in rats.Thirty Wistar albino female rats were randomized to three groups (n=10 in each group): Group-I as the control group, Group-II as the arthritis group, Group-III as the lapatinib group were assigned. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant in Group-II and III rats. One day after the onset of arthritis, Group-III rats were given lapatinib (30 mg/kg/day) via oral gavage until they were killed on day 29. The trunk bloods and paws of the rats were obtained for further analysis. Tumor necrosis factor (TNF)-?, interleukin (IL)-17, malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities in serum, and articular tissue nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxgenase-1 (HO-1) expressions, perisynovial inflammation and cartilage-bone destruction were determined in the paws.When compared with Group-I, TNF-?, IL-17, and MDA levels were increased, and SOD, CAT, GPx activities and the expressions of Nrf2 and HO-1 were decreased in Group-II. Histopathological analysis demonstrated the extensive perisynovial inflammation and marked cartilage-bone destruction in Group-II rats. Lapatinib treatment decreased the levels of TNF-?, IL-17, MDA, and increased the activities of SOD, CAT, GPx and the expressions of Nrf2 and HO-1, and decreased the perisynovial inflammation and cartilage-bone destruction in the paws.Conclusion: Our present study is the first report to identify that lapatinib suppresses inflammatory pathways and oxidative stress, and prevents synovial hyperplasia in CIA model. Lapatinib may be an effective option for the treatment of RA.