M Iida1, K Saito. 1. Research and Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Abstract
OBJECTIVE AND DESIGN: 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. MATERIAL AND TREATMENT: 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.
OBJECTIVE AND DESIGN: 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. MATERIAL AND TREATMENT: Male rats were treated with saline (n=8-10), recombinant humanSOD (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 ratinflammation models, and endotoxin-like contaminants may have contributed to some protective effects of SOD administration in previous studies.
Authors: Fons A J van de Loo; Miranda B Bennink; Onno J Arntz; Ruben L Smeets; Erik Lubberts; Leo A B Joosten; Peter L E M van Lent; Christina J J Coenen-de Roo; Salvatore Cuzzocrea; Brahm H Segal; Steven M Holland; Wim B van den Berg Journal: Am J Pathol Date: 2003-10 Impact factor: 4.307