Combination of melatonin and chondroitin sulphate provides better chondroprotection in osteoarthritis in male Wistar rats

Purpose: To investigate the effect of melatonin (MEL) and chondroitin sulphate (CHS) in osteoarthritis (OA) in male Wistar rats. Methods: A total of 42 Wistar rats (175 - 200 g) were divided randomly into 7 groups (n = 6) including control (received 0.5 mL normal saline orally), sham (received 0.5 mL of normal saline intra-articularly, osteoarthritis-induced (OA; received 2 mg monoiodoacetate intra-articularly) and OA treated groups (CHS: received 300 mg/kg CHS orally, MEL: received 100 mg/kg MEL orally, CHS and MEL: received300 mg/kg CHS and 100 mg/kg ME orally), and positive control (diclofenac: received 2 mg/kg diclofenac orally). After 21 days of daily oral treatment, blood samples were obtained via retro-orbital collection, and the synovial fluid was collected and used for biochemical analysis. The matrix metalloproteinases-13 (MMP-13) gene expression and immunohistochemical analysis of collagen type2 (COL-2) were also carried out on the cartilage. Results: Osteoarthritis-induced group showed significantly lower levels of antioxidant enzymes and Bcl2, and significantly higher levels of pro-inflammatory markers, caspase-3, ADAMTS-5 levels, and upregulation in mRNA expression of MMP-13 compared to control and treated groups (p < 0.05). Also, treatment with MEL plus CHS significantly reversed down-regulation of COL-2 induced in OA group (p <0.05).Conclusion: Combination of CHS and MEL significantly improves outcomes, lowers levels of proinflammatory markers, interleukins, caspase-3, and downregulates MMP-13 gene expression compared to either CHS, MEL, or diclofenac alone in osteoarthritis-induced Wistar rats.