Inhibition by rhein of nitrosothiol production of human chondrocytes from osteoarthritis in culture

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 generate in nitrite or nitrate. High concentrations of these metabolites have been found in sera and synovial fluids from patients with osteoarthritis, the higher synovial concentrations suggesting NOo intra-articular production. The aim of this study was to evaluate the capacity of osteoarthritic chondrocytes to produce bioactive NOo metabolites and to study the inhibitory effect 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 rhein (1.3 x 10-5, 6.5 x 10-6, 1.3 x 10-6 M) or diclofenac (10-5, 10-6 M). After 24 hours, nitrite and nitrosothiols were measured in the supernatants and nitrosothiols were also determined in cell lysats. After interleukin-1 beta stimulation chondrocytes produced great quantities of nitrosothiols and nitrite. This effect was inhibited in a dose dependent manner by rhein but not by diclofenac. In conclusion, chondrocytes produce high quantities of nitrosothiols after IL-1 beta stimulation and this effect is inhibited by rhein. This drug could be beneficial to prevent the destruction of osteoarthritic cartilage.