Antiarthritic activity of the newly developed neutrophil oxidative burst antagonist apocynin.
The plant-phenol 4-hydroxy-3-methoxyacetophenone (trivial name apocynin) is a strong inhibitor of neutrophil superoxide anion (O2-) release in vitro. In vitro the inhibitory effect of apocynin is restricted to cells with the capacity to release peroxidase and reactive oxygen species (ROS). Peroxidase deficient cells are insensitive to apocynin. In the present study the antiinflammatory activity of apocynin was tested in collagen-induced arthritis in rats. Collagen-immunized rats were treated with different doses of apocynin in the drinking water starting at the onset of joint-swelling and terminating 14 days later, at the time when joint swelling in the control group was maximal. Apocynin-treated animals had a normal plasma level of collagen-specific antibodies, but showed a significant reduction of the joint swelling. Also the plasma IL-6 level in apocynin-treated animals was substantially lower than in control animals. No flare-up of joint swelling after termination of the treatment was observed in the apocynin-treated groups.
't Hart
B A
BA
Department of Chronic and Infectious Diseases, TNO Institute for Applied Radiobiology and Immunology, Rijswijk, The Netherlands.
Simons
J M
JM
Knaan-Shanzer
S
S
Bakker
N P
NP
Labadie
R P
RP
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D003094:Collagen / Q000276:immunology / Q000633:toxicity; D005609:Free Radicals; D007074:Immunoglobulin G / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism
D000098:Acetophenones; D005609:Free Radicals; D007074:Immunoglobulin G; D015850:Interleukin-6; D013481:Superoxides; D003094:Collagen; C056165:acetovanillone; D010100:Oxygen