Family of naturally occurring metalloenzymes that act as free oxygen radical scavengers and protect against the deleterious effects of biologically generated superoxide oxygen radicals (O2.) by dismutation to hydrogen peroxide (H2O2) + molecular oxygen (O2). Three metallotypes have been described; distinguished by the metal found at the active site: cupro-zinc containing (Cu/Zn SOD), manganese containing (Mn SOD), and iron containing (Fe SOD). Widely distributed, present in almost all aerobic organisms and some anaerobes. Isoln and purification of Cu/Zn SOD from bovine erythrocytes and identity with erythrocuprein (hemocuprein): J. M. McCord, I. Fridovich, J. Biol. Chem. 244, 6049 (1969); of Mn SOD from E. coli: B. B. Keele et al., ibid. 245, 6176 (1970); of Fe SOD from E. coli: F. J. Yost, Jr., I. Fridovich, ibid. 248, 4905 (1973). Enzyme immunoassay for determn of human Cu/Zn SOD: N. Kurobe et al., Clin. Chim. Acta 187, 11 (1990); of human Mn SOD: idem et al., ibid. 192, 171 (1990). Review of biological activity and therapeutic use: A. Petkau, Cancer Treat. Rev. 13, 17-44 (1986); of protective effect vs radiation injury: eidem, Br. J. Cancer 55, Suppl. 8, 87-95 (1987); of structure and function: J. V. Bannister et al., Crit. Rev. Biochem. 22, 111-180 (1987); of chemical and biological characteristics: B. A. Omar et al., Adv. Pharmacol. 23, 109-161 (1992). Books: Superoxide and Superoxide Dismutases, A. M. Michelson et al., Eds. (Academic Press, New York, 1977) 568 p.; Superoxide Dismutase vols. I, II, III, L. W. Oberley, Ed. (CRC Press, Inc., Boca Raton, 1982, 1982, 1985).
Water-soluble Cu/Zn SOD produced from beef liver. Mol wt ≈33,000 with a compact conformation maintained by about 4 gram atoms of chelated divalent metal. Isoln: W. Huber, ZA 6902983; idem, US 3579495 (1969, 1971 both to Diagnostic Data). Purification: idem, DE 2101866; idem, US 3624251 (both 1971 to Diagnostic Data). Toxicology: S. Carson et al., Toxicol. Appl. Pharmacol. 26, 184 (1973). Clinical pharmacokinetics: G. Jadot et al., Clin. Pharmacokinet. 28, 17 (1995). Clinical studies in osteoarthritis: K. Lund-Olesen, K. B. Menander-Huber, Arzneim.-Forsch. 33, 1199 (1983); in Peyronie's disease: G. Primus, Int. Urol. Nephrol. 25, 169 (1993). Clinical use of liposomal form vs radiation-induced fibrosis: S. Delanian et al., Radiother. Oncol. 32, 12 (1994). Therapeutic use in animals: D. E. Breshears et al., Mod. Vet. Pract. 55, 85 (1974); S. Ahlengard et al., Equine Vet. J. 10, 122 (1978); J. R. Coffman et al., J. Am. Vet. Med. Assoc. 174 261 (1979). Review of clinical trials: L. Flohé, Mol. Cell. Biochem. 84, 123-131 (1988).
Orgotein polyethylene glycol conjugate; mol wt 71-105 kDa. Prepn and anti-inflammatory activity: P. S. Pyatak et al., Res. Commun. Chem. Pathol. Pharmacol. 29, 113 (1980). Pharmacokinetics: E. Boccu et al., Pharmacol. Res. Commun. 14, 113 (1982). Toxicology: A. T. Viau et al., J. Free Radicals Biol. Med. 2, 283 (1986). Clinical trials in head injury: J. P. Muizelaar, Adv. Exp. Med. Biol. 366, 389 (1994).
Pharmacokinetics: C. Tsao et al., Clin. Pharmacol. Ther. 50, 713 (1991). Clinical study in renal transplantation: W. Land et al., Transplantation 57, 211 (1994). Review of cloning and expression: D. Tuoati, Free Radical Biol. Med. 5, 393-402 (1988).
Anti-inflammatory; radioprotective agent.
Anti-inflammatory (Nonsteroidal)