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Reactive nitrogen species scavenging, rather than nitric oxide inhibition, protects from articular cartilage damage in rat zymosan‐induced arthritis
Author(s) -
Bezerra Mirna Marques,
Brain Susan D,
Greenacre Stan,
Jerônimo Selma Maria Bezerra,
De Melo Liana Batista,
Keeble Julie,
Da Rocha Francisco Airton Castro
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705600
Subject(s) - nitric oxide , zymosan , chemistry , synovitis , nitric oxide synthase , nitrotyrosine , arthritis , pharmacology , proinflammatory cytokine , peroxynitrite , glycosaminoglycan , endocrinology , reactive nitrogen species , medicine , inflammation , biochemistry , superoxide , enzyme , organic chemistry , in vitro
The contribution of nitric oxide (NO) and peroxynitrite (PN) to inflammation in a zymosan‐induced (1 mg, intra‐articular, i.art.) rat model of arthritis was assessed by histopathology and by measuring the glycosaminoglycan (GAG) content of the articular cartilage. Progression of the chronic synovitis in zymosan‐induced arthritis (ZYA) was associated with increased nitrite and nitrotyrosine (3‐NT) levels in the joint exudates that paralleled a progressive loss of the GAG content. An increase in 3‐NT was also observed after i.art. PN. The nonselective nitric oxide synthase (NOS) inhibitor L ‐ N G ‐nitroarginine methyl ester (25–75 mg kg −1 day −1 ) or the selective inducible NOS inhibitor aminoguanidine (50–100 mg kg −1 day −1 ) given 1 h before (prophylactic) or 3 days after (therapeutic) injection of the zymosan ameliorated the synovitis, but worsened the GAG loss, as measured at the end of the experiment (day 7). The PN scavenger uric acid (100–250 mg kg −1 i.p. four times daily) given prophylactically until the end of the experiment (day 14), in a dose compatible with its PN scavenging activity, significantly decreased both the synovitis and the GAG loss. In conclusion, PN formation is associated with cartilage damage in addition to proinflammatory activity in ZYA. NOS inhibitors and a PN scavenger were able to reduce the cellular infiltration, while displaying opposite effects on cartilage homeostasis either by enhancing or ameliorating the damage, respectively.British Journal of Pharmacology (2004) 141 , 172–182. doi: 10.1038/sj.bjp.0705600