Attenuation of adjuvant arthritis in rats by treatment with oxygen radical scavengers

Abstract

SummaryThe 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-Dawiey (SD) rats by a single intradermal (i.d.) injection o'i Mycobacteriwn tuhcrctilosis (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-cells). In contrast, spontaneous OH-production by normal circulating leucocytes was absent (0.07±0.03 OH-units/h per 10^ 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 1 1. 12 and 13 postadjuvant injection. Both DMTU and DMSO significantly reduced the clinical evidence of arthritis ells/four joints, /"< 0.01 compared with disease control = 11.76 ± 1.7 x 10^ cells/four joints). Neither treatment inhibited cutaneous delayed type hypersensitivity (DTH) to the disease inducing antigen. Furthermore, DMTU (500 mg/kg) did not cause neutropenia nor inhibit peritoneal neutrophil accumulation in response to a chemotactic stimulus. This study demonstrates the attenuation of adjuvant arthritis by ROS scavengers and suggests a pivotal role for ROS, particularly 0H-, in the mediation of joint inflammation in this disease.

Dual effect of nitric oxide donor on adjuvant arthritis

“…In this study, signs and symptoms of rheumatoid arthritis did not appear in contralateral non-injected hind paw after CFA inoculation so, the method of induction of adjuvant arthritis was modified by intradermal inoculation of squalene in addition to CFA into the subplanter surface of right hind paw, to increase sensitivity of arthritic rats to CFA. Squalene was also used by others to potentiate the effect of CFA [36]. The present study demonstrated protective and deleterious effects for SNP administration on the local inflammatory infiltrate in the adjuvant arthritic rats.…”

Hemoglobin protects from streptococcal cell wall-induced arthritis

“…Joint tissues from control, arthritic, and Hgb-treated rats were excised and fixed in 10% buffered formalin, decalcified in 10% EDTA, embedded in paraffin, sectioned (6), and stained with hematoxylin and eosin for histologic examination. Immunohistochemical staining for iNOS was performed using isoform-specific anti-iNOS antibody (diluted 1:200, overnight at 4°C; Upstate Biochemical, Lake Placid, NY).…”

“…However, in pathologic conditions often associated with acute and chronic inflammatory responses, if cellular antioxidant defenses are overwhelmed, bypassed, or inactivated, autotoxicity may ensue. Joint inflammation, in animal models (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and in humans (16)(17)(18)(19)(20), represents a prototype of phagocyteoxidant-dependent pathology.…”

Vitamin E uncouples joint destruction and clinical inflammation in a transgenic mouse model of rheumatoid arthritis

“…There is no good animal model of RA (14)(15)(16)(17). The most widely used is the murine model of collageninduced arthritis, which was established 25 years ago.…”