Failure of endotoxin-free superoxide dismutase to reduce some paw edemas and adjuvant arthritis in rats.
OBJECTIVE
To elucidate whether superoxide anion plays a major role in inflammation models in rats. Endotoxin-free CuZn superoxide (SOD) was used in the present study, because we had shown previously that even a trace of endotoxin contamination of SOD would carry anti-inflammatory effects.


METHODS
Male rats were treated with saline (n=8-10), recombinant human SOD (n=8-10), and dexamethasone or indomethacin (n=8-10).


METHODS
Foot volume was determined by mercury displacement.


RESULTS
Two administrations of SOD (5 and 50 mg/kg), 2 h and just before irritant injection, had no effect on rat paw edema induced by phorbol, zymosan or carrageenan. Two administrations of dexamethasone (1 mg/kg) or indomethacin (3 mg/kg), 2 h and just before irritation, inhibited paw edema significantly (p<0.05). Administration of SOD (10 mg/kg) once daily for 3 weeks from the day of mycobacterium injection had no effect on injected paw swelling and non-injected paw swelling 7, 14, 21 days after irritation. Indomethacin (2 mg/kg) once daily for 3 weeks inhibited this arthritis significantly (p < 0.05).


CONCLUSIONS
Superoxide anion may not play a major role in the genesis of inflammation in these rat inflammation models, and endotoxin-like contaminants may have contributed to some protective effects of SOD administration in previous studies.
Iida
M
M
Research and Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Saito
K
K
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D004487:Edema / Q000188:drug therapy*; D004731:Endotoxins / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D004731:Endotoxins; D011994:Recombinant Proteins; D013482:Superoxide Dismutase