Abstract
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 asEscherichia 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.
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References
Ōyanagui Y. Participation of superoxide anions at the prostaglandin phase of carrageenan foot-oedema. Biochem Pharmacol 1976;25:1465–72.
Huber W, Menander-Huber KB, Saifer MGP, Dang PH-C. Studies on the clinical and laboratory pharmacology of drug formulations of bovine Cu−Zn superoxide dismutases (orgotein). In: Willoughby DA, Giroud JP, Velo GP, editors. Perspectives in Inflammation: Future trends and Developments. Baltimore: University Park Press, 1977:527–44.
Borrelli F, Serafini C, Mattalia G, Caprino L. Additional pharmacological aspects of orgotein, a metalloprotein with superoxide-dismutase activity. Arzneim Forsch/Drug Res 1979;29:781–5.
Ōyanagui Y. Steroid-like anti-inflammatory effect of superoxide dismutase in sertonin-, histamine- and kinin-induced edemata of mice: Existance of vascular permeability regulating protein(s). Biochem Pharmacol 1981;30:1791–8.
McCormick JR, Harkin MM, Johnson KJ, Ward PA. Suppression by superoxide dismutase of immune-comlex-induced pulmonary alveolitis and dermal inflammation. Am J Pathol 1981;102:55–61.
Baret A, Jadot G, Michelson AM. Pharmacokinetic and antiinflammatory properties in the rat of superoxide dismutases (Cu SODs and Mn SOD) from various species. Biochem Pharmacol 1984;33:2755–60.
Yoshikawa T, Tanaka H, Kondo M. The increase of lipid peroxidation in rat adjuvant arthritis and its inhibition by superoxide dismutase. Biochem Med 1985;33:320–6.
Michelson AM, Jadot G, Puget K. Mechanism of anti-inflammatory activity of superoxide dismutases. In: Hayashi O, Imamura S, Miyachi Y, editors. The Biological Role of Reactive Oxygen Species in Skin. Tokyo: University of Tokyo Press, 1987:199–210.
Vaille A, Jadot G, Elizagaray A. Anti-inflammatory activity of various superoxide dismutases on polyarthritis in the Lewis rat. Biochem Pharmacol 1990;39:247–55.
Oyanagui Y, Sato S. Opposite effect of superoxide disumutase, L-arginine analogues, methylene blue and desferal: Supperssion of histamine-induced and stimulation of serotonin-induced paw edema in mice. Biol Signals 1993;2:37–44.
Neychev H, Ivanovska N, Valeva V, Stefanova Z, Kuyumdjieva A. Antiinflammatory effect of superoxide dismutase (SOD): Comparison between yeast and bovine SOD on some complement-mediated reactions in vitro and in vivo. Int J Tiss Reac 1994;16:131–7.
Oyanagui Y. Nitric oxide and superoxide radical are involved in both initiation and development of adjuvant arthritis in rats. Life Science 1994,54:285–9.
Shingu M, Takahashi S, Ito M, Hamamatu N, Suenaga Y, Ichibangase Y, et al. Anti-inflammatory effects of recombinant human manganese superoxide dismutase on adjuvant arthritis in rats. Rheumatol Int 1994;14:77–81.
Hirschelmann R, Bekemeier H. Effects of catalase, peroxidase, superoxide dismutase and 10 scavengers of oxygen radicals in carrageenin edema and in adjuvant arthritis of rats. Experientia 1981;37:1313–4.
Iwanaga S, Morita T, Harada T, Nakamura S, Niwa M, Takada K, et al. Chromogenic substrates for Horseshoe Crab clotting enzyme: Its application for the assay of bacterial endotoxins. Haemostasis 1978;17:183–8.
McCord JM, Fridovich I. Superoxide dismutase: An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 1969;244:6049–55.
Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research. Circ Res 1980;47:1–9.
Huber W, Menander-Huber KB. Orgotein. Clin Rheum Dis 1980;6:465–98.
Veronese FM, Boccu E, Schiavon O, Velo GP, Conforti A, Franco L, et al. Anti-inflammatory and pharmacokinetic properties of superoxide dismutase derivatized with polyethylene glycol via active esters. J Pharm Pharmacol 1983;35: 757–8.
Jones HP, Grisham MB, Bose SK, Shannon VA, Schott A, McCord JM, Effect of allopurinol on neutrophil superoxide production, chemotaxis, or degranulation. Biochem Pharmacol 1985;34:3673–6.
Maguire ED, Wallis RB. The role of bacterial contamination in the isolation of apparent anti-inflammatory factors from rabbit anti-lymphocytic serum. Br J Pharmac 1977;59:261–8.
Bito LZ. Inflammatory effects of endotoxin-like contaminants in commonly used protein preparations. Science 1977;196: 83–5.
Frank L, Yam J, Roberts RJ. The role of endotoxin in protection of adult rats from oxygen-induced lung toxicity. J Clin Invest 1978;61:269–75.
Gordon T, Milligan SA, Levin J, Thompson JE, Fine JM, Sheppard D. Apparent effect of catalase on airway edema in guinea pigs: Role of endotoxin contamination. Am Rev Respir Dis 1987;135:854–9.
Lund-Olesen K, Menander-Huber KB. Intra-articular orgotein therapy in osteoarthritis of the knee: A double-blind, placebo-controlled trial. Arzneim Forsch/Drug Res 1983;33:1199–203.
Smith MJH, Ford-Hutchinson AW, Walker JR. Anti-inflammatory activity of bacterial endotoxin. J Pharmacol 1977;29:702–5.
Verghese MW, Synderman R. Differential anti-inflammatory effects of LPS in susceptible and resistant mouse strains. J Immunol 1981;127:288–93.
Hollinger MA, Patwell SW, Zukerman JE. Effect of endotoxin on thiourea induced polumonary edema and pleural effusion. Res Commun Chem Pathol Pharmacol 1981;31:217–22.
Rosenbaum JT, Hartiala KT, Webster RO, Howes EL, Goldstein IM. Antiinflammatory effects of endotoxin: Inhibition of rabbit polymorphonuclear leukocyte responses to complement (C5)-derived peptides in vivo and in vitro. Am J Pathol 1983;113:291–9.
Rosenbaum JT, Mandell RB. The effect of endotoxin and endotoxin tolerance on inflammatory induced by mycobacterial adjuvant. Yale J Biol Med 1983;56:293–301.
Allen CA, Ferry DM, Chadwick VS. Anti-inflammatory effects of LPS, MDP and FMLP on carrageenan pleurisy in the rat. Agents Actions 1994;41:53–6.
Hartiala KT, Langlois L, Goldstein IM, Rosenbaum JT. Endotoxin-induced selective dysfunction of rabbit polymorphonuclear leukocytes in response to endogenous chemotactic factors. Infect Immun 1985;50:527–33.
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Iida, M., Saito, K. Role of endotoxin-like contaminants in the apparent anti-inflammatory activity of bovine superoxide dismutase. Inflamm Res 45, 268–271 (1996). https://doi.org/10.1007/BF02280989
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DOI: https://doi.org/10.1007/BF02280989