期刊
OSTEOARTHRITIS AND CARTILAGE
卷 9, 期 1, 页码 1-6出版社
W B SAUNDERS CO LTD
DOI: 10.1053/joca.2000.0353
关键词
nitrosothiols; nitric oxide; osteoarthritis; chondrocyte; rhein
Objective: Nitric oxide (NO degrees) is a free molecule produced by NO synthases which acts as a mediator in inflammatory processes. NO degrees can react with thiol groups of proteins to produce nitrosothiols. increased concentrations of these bioactive compounds have been found in sera and synovial fluids from patients with osteoarthritis (OA). The aim of this study was to assess the ability of human osteoarthritic chondrocytes to synthesize nitrosothiols and to compare the in vitro effects of rhein, cortisol and diclofenac on nitrosothiol and nitrite production. Methods: Osteoarthritic chondrocytes were incubated for 24 h with 1 ng/ml of recombinant human interleukin-1 beta (IL-1 beta) in the presence or absence of rhein (1.3x10(-5) M, 6.5x10(-6) M, or 1.3x10(-6) M), cortisol (10(-5) M) or diclofenac (10(-5) M or 10(-6) M). Nitrite levels were measured in cell supernatants by the Griess method; nitrosothiol levels were determined in supernatants and cellular lysates by fluorimetry. Results: At the basal level, nitrosothiols represented 80% of the total of nitrite and nitrosothiol production. After IL-1 beta stimulation, NO degrees production was highly increased in the supernatants (45-fold increase in nitrite, 60-fold increase in nitrosothiols) as well as in cell lysates (35-fold increase in nitrosothiols). Rhein caused a dose-dependent decrease in nitrosothiol and nitrite production. In comparison. diclofenac (10(-5) M) moderately decreased nitrite and nitrosothiol levels in the supernatants but had no effect on lysate nitrosothiol. Cortisol had no significant effect on NO degrees production. Conclusions: The IL-1 beta stimulation increased nitrosothiol production by osteoarthritic chondrocytes. These results demonstrate the need to measure nitrosothiol as well as nitrite production. Rhein inhibited the IL-1 degrees induced NO degrees production, and may be a suitable treatment for osteoarthritis. (C) 2001 OsteoArthritis Research Society International.
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