Attenuation of adjuvant arthritis in rats by treatment with oxygen radical scavengers.
The contribution of reactive oxygen species (ROS), in particular hydroxyl radical (OH.), to joint inflammation was examined in rats developing adjuvant arthritis (AA) by treatment with ROS scavengers dimethylthiourea (DMTU) and DMSO. Adjuvant arthritis was induced in Sprague-Dawley (SD) rats by a single intradermal (i.d.) injection of Mycobacterium tuberculosis (MT) in oil on day 0. By day 14, all rats exhibited arthritis in the hindlimbs and the majority had involvement of the forelimbs. A marked inflammatory cell influx (75% neutrophils) was present in the synovial fluid. These cells, in vitro, spontaneously produced OH. (0.96 +/- 0.28 OH. units/h per 10(5) cells). In contrast, spontaneous OH. production by normal circulating leucocytes was absent (0.07 +/- 0.03 OH. units/h per 10(5) cells). Adjuvant-injected rats were treated with DMTU (500, 250 and 100 mg/kg), DMSO (330 and 165 mg/kg) or saline (disease control) once daily on days 8, 9 and 10 and twice daily on days 11, 12 and 13 postadjuvant injection. Both DMTU and DMSO significantly reduced the clinical evidence of arthritis (clinical scores: DMTU [500 mg/kg] = 0, P < 0.0001; DMSO [3.0 mL/kg] = 0.4 +/- 0.3, P < 0.01, compared with disease control = 2.3 +/- 0.3). Synovial fluid cell accumulation was also significantly reduced (DMTU [500 mg+kg] = 0.5 +/- 0.1 x 10(5) cells/four joints, P < 0.0001; DMSO [3.0 mL/kg] 2.75 +/- 1.9 x 10(5) cells/four joints, P < 0.01 compared with disease control = 11.76 +/- 1.7 x 10(5) cells/four joints). Neither treatment inhibited cutaneous delayed type hypersensitivity (DTH) to the disease inducing antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
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D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D002634:Chemotaxis, Leukocyte; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006614:Hindlimb; D007958:Leukocyte Count; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C038983:1,3-dimethylthiourea; D013890:Thiourea; D004121:Dimethyl Sulfoxide