1. The aim of the present study was to investigate the effects of
cloricromene, a
coumarine derivative, in rats subjected to
collagen-induced arthritis. 2.
Collagen-induced arthritis (CIA) was induced in Lewis rats by an
intradermal injection of 100 microl of the
emulsion (containing 100 microg 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. 3. 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. 4. 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. 5. 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. 6. Radiographic signs of protection against
bone resorption and
osteophyte formation were present in the joints of
cloricromene-treated rat. 7. 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.