Rheine-inhibition of nitrosothiols production from cultured human chondrocytes

Nitric oxide (NOo) is an inorganic radical produced after the activation of a NO synthase involved in inflammatory and immune reactions. It can react with protein thiols to form nitrosothiols, a bioactive molecule or can gene rate in nitrite or nitrate. High concentrations of these metabolites have b een found in sera and synovial fluids from patients with osteoarthritis, th e higher synovial concentrations suggesting No-o intra-articular production . The aim of this study was to evaluate the capacity of osteoarthritic chon drocytes to produce bioactive NOo metabolites and to stud the inhibitory ef fect of rhein, the active form of diacerhein. Chondrocytes were stimulated by interleukin-1 beta (1 ng/ml) during 24 hours in presence or absence of r hein (1.3x10-5, 6.5x10-6, 1.3x10-6 M) or diclofenac (10-5, 10-6 M). After 2 4 hours, nitrite and nitrosothiols were measured in the supernatants and ni trosothiols ere also determined in cell lysats. After interleukin-1 beta st imulation chondrocytes produced great quantities of nitrosothiols and nitri te. This effect was inhibited ina doe dependent manner by rhein but not by diclofenac. In conclusion, chondrocytes produce high quantities of nitrosot hiols after IL-1 beta stimulation and this effect is inhibited by rhein. Th is drug could be beneficial to prevent the destruction of osteoarthritic ca rtilage.