Role of endotoxin-like contaminants in the apparent anti-inflammatory activity of bovine superoxide dismutase.
Bovine CuZn superoxide dismutase (SOD: 1, 3 and 10 mg/kg) dose-dependently reduced carrageenan-induced paw edema in rats when administered intravenously 30 min before irritant injection. However, heat-treated SOD (10 mg/kg) was as effective as native SOD (10 mg/kg) although the enzymic activity was reduced to 9.7%. Examination of the contaminants of the native SOD revealed a fairly large amount of endotoxin-like activity, 47 ng as Escherichia coli endotoxin per mg, and 59.6% of this activity remained after heat treatment. Bovine CuZn SOD (1, 3 and 10 mg/kg), which contained negligible endotoxin-like materials and 1.5 times more enzyme units, had no effect on edema under the same conditions. Furthermore, Escherichia coli endotoxin (10, 100 and 1000 ng/kg) reduced edema dose-dependently. These results suggest that contamination by endotoxin-like materials is responsible for the anti-inflammatory action of the SOD preparation we observed. Hence, the anti-inflammatory action of contaminating endotoxin-like materials may lead to misinterpretation as a protective effect of SOD unless stringent precautions are taken against endotoxin-like contaminants in the SOD under examination.
Iida
M
M
Research and Development Division, Nippon Kayaku Co. Ltd., Tokyo, Japan.
Saito
K
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000008:administration & dosage / Q000633:toxicity; D002417:Cattle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004356:Drug Storage / Q000592:standards*; D004487:Edema / Q000188:drug therapy*; D004731:Endotoxins / Q000378:metabolism* / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013696:Temperature
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D002351:Carrageenan; D013482:Superoxide Dismutase