Safety evaluation of free radical scavengers PEG-catalase and PEG-superoxide dismutase.
Treatment with catalase and SOD (superoxide dismutase) could diminish the damage due to oxygen free radical formation, but these enzymes are rapidly removed from circulation. The covalent attachment of monomethoxypolyethylene glycol (PEG) to catalase and SOD extended their plasma half-lives. Toxicity of PEG-catalase and PEG-SOD was evaluated in mice and rats prior to their use as free radical scavengers. Rodents used in acute, subacute, and subchronic toxicologic studies could tolerate large doses of PEG-catalase and PEG-SOD without developing toxic signs. The conjugates did not affect survival rate, appearance, behavior, food intake, blood chemistry, hematology, or urinalysis. In general, body weight gains, organ weights, and histomorphology were also unaffected. Massive doses of PEG-catalase caused slight weight loss, splenic hypertrophy, and generalized splenic stimulation in mice. Massive doses of PEG-SOD resulted in vacuolation in splenic macrophages in rats. PEG-catalase and PEG-SOD circulated for 3 days and 8 days, respectively, in mice following i.v. or i.m. administration.
D000818:Animals; D001773:Blood Cells; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000097:blood / Q000633:toxicity* / Q000652:urine; D004435:Eating / Q000187:drug effects; D005260:Female; D005609:Free Radicals; D006207:Half-Life; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000097:blood / Q000633:toxicity* / Q000652:urine; D051381:Rats; D013482:Superoxide Dismutase / Q000097:blood / Q000633:toxicity* / Q000652:urine; D014556:Urine
D005609:Free Radicals; D011092:Polyethylene Glycols; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen