Silymarin potentiates the anti-inflammatory effects of Celecoxib on chemically induced osteoarthritis in rats

Silymarin (SMN) is used as an antioxidant complex to attenuate the pro-oxidant effects of toxic agents. This study was carried out to investigate the effect of SMN, Celecoxib (CLX) individually and in combination on monoiodoacetate (MIA)-induced osteoarthritis (OA) in rat. Forty adult Wistar rats were assigned to control and test groups. Animals in the test group following OA induction were subdivided into 4 subgroups according to the treatment profile: OA(+); received saline normal (5 ml/kg, b.w.), OA(+)CLX(+); received CLX (100 mg/kg, orally), OA(+)SMN(+), received SMN (50 mg/kg, orally), and OA(+)CLX(+)SMN(+), received both CLX and SMN. The animals received test compounds by gastric gavage for 14 consecutive days. Animals in the OA(+) group showed a significant (p < 0.01) increase in serum and synovial levels of IL-1 beta, while both test compounds reduced the IL-1 beta level. Both CLX and SMN lowered the OA-increased level of malondialdehyde by 77% and 79% and nitric oxide by 73% and 76%, respectively, in the synovial tissue. Special safranin O (SO) histopathological staining revealed that CLX and SMN improved the MIA-induced destruction and fibrillation in cartilage surface. CLX and SMN regulated the MIA-up regulated IL-1 beta at mRNA level. The combination therapy resulted in an additive effect between CLX and SMN in biochemical, histopathological and molecular assays. These findings suggest that SMN exerts anti-inflammatory effect and also potentiates the anti-inflammatory effect of CLX on MIA-induced OA. The anti-inflammatory property of SMN may attribute to its antioxidant capacity, which affects the proinflammatory mediators at translational and transcriptional level. (c) 2012 Elsevier GmbH. All rights reserved.