Beneficial effects of tempol, a membrane-permeable radical scavenger, in a rodent model of collagen-induced arthritis.
OBJECTIVE
To investigate the effects of tempol, a membrane-permeable radical scavenger, in rats with collagen-induced arthritis (CIA).


METHODS
CIA was induced in Lewis rats by intradermal injection of 100 microl of an emulsion of 100 microg of bovine type II collagen (CII) in complete Freund's adjuvant (FCA) at the base of the tail. On day 21, a second injection of CII in FCA was administered.


RESULTS
Lewis rats developed an erosive arthritis of the hind paws when immunized with CII in FCA. Macroscopic evidence of CIA first appeared as periarticular erythema and edema 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. Radiographs revealed focal resorption of bone, with osteophyte formation in the tibiotarsal joint, and soft tissue swelling. The histopathologic features included erosion of the cartilage at the joint margins. Treatment of rats with tempol (10 mg/kg/day intraperitoneally) starting at the onset of arthritis (day 23) delayed the development of the clinical signs on days 24-35 and improved the histologic status of the knee and paw. Immunohistochemical analysis for nitrotyrosine and poly(ADP-ribose) synthetase (PARS) revealed positive staining in the inflamed joints of CII-treated rats. The degree of nitrotyrosine and PARS staining was markedly reduced in tissue sections obtained from CII-treated rats that had received tempol. Furthermore, radiographs revealed protection against bone resorption and osteophyte formation in the joints of tempol-treated rats.


CONCLUSIONS
This study is the first to provide evidence that tempol, a small molecule that permeates biologic membranes and scavenges reactive oxygen species, attenuates the degree of chronic inflammation and tissue damage associated with CIA in the rat.
Cuzzocrea
S
S
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Italy.
McDonald
M C
MC
Mota-Filipe
H
H
Mazzon
E
E
Costantino
G
G
Britti
D
D
Mazzullo
G
G
Caputi
A P
AP
Thiemermann
C
C
D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001835:Body Weight / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D007700:Kinetics; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013113:Spin Labels; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; C002744:3-nitrotyrosine; D014443:Tyrosine; D011065:Poly(ADP-ribose) Polymerases; C001803:tempol