Abstract: AIM: To study the effect and mechanism of A771726, the active metabolite of leflunomide, on the production of nitric oxide (NO) of peritoneal macrophages (PMФ) from collagen-induced arthritis (CIA) rats. METHODS: Collagen-induced arthritis (CIA) model was induced in rats and the PMФ were collected. A771726 were used in vitro. The dose-dependent and time-dependent effects of A771726 on the secretion of NO of PMФ from CIA rats were checked by nitric acid reduction synthase method; MTT reagent was used to detect the effect of A771726 on the cell viability of PMФ from CIA rats; RT-PCR was used to detect the expression of inducible NO synthase (iNOS) mRNA. Western blot was used to detect the expression of iNOS protein. RESULTS: A771726 could inhibit the secretion of NO of PMФ from CIA rats in a dose-dependent and time-dependent manner. The cytotoxicity of A771726 was not detected during the time course and dose range. A771726 (0.1, 1, 10 mol/L) significantly inhibited the expression of iNOS mRNA and iNOS protein in PMФ from CIA rats. CONCLUSION: A771726 (0.1, 1, 10 mol/L) can inhibit the transcription of iNOS mRNA in PMФ from CIA rats, and reduce the translation of iNOS protein, which leads to suppressing the secretion of NO. And the suppression is not related to the cytotoxicity of A771726.

Key words: A771726, Arthritis, Macrophages, iNOS