Cloricromene, a coumarine derivative, protects against collagen‐induced arthritis in Lewis rats

The aim of the present study was to investigate the effects of cloricromene, a coumarine derivative, in rats subjected to collagen‐induced arthritis. Collagen‐induced arthritis (CIA) was induced in Lewis rats by an intradermal injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Lewis rats developed an erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri‐articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII challenged rats and the severity of CIA progressed over a 35‐day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of rats with cloricromene (10 mg kg−1 i.p. daily) starting at the onset of arthritis (day 23), delayed the development of the clinical signs at days 24–35 and improved histological status in the knee and paw. Immunohistochemical analysis for iNOS, COX‐2, nitrotyrosine and for poly (ADP‐ribose) synthetase (PARS) revealed a positive staining in inflamed joints from collagen‐treated rats. The degree of staining for iNOS, COX‐2, nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen‐treated rats, which had received cloricromene. Radiographic signs of protection against bone resorption and osteophyte formation were present in the joints of cloricromene‐treated rat. This study provides the first evidence that cloricromene, a coumarine derivative, attenuates the degree of chronic inflammation and tissue damage associated with collagen‐induced arthritis in the rat. British Journal of Pharmacology (2000) 131, 1399–1407; doi:10.1038/sj.bjp.0703695