title: Intravascularly administered crosslinked immunoprecipitates of gulonolactone oxidase are toxic and rapidly cleared from the circulation.
abstract: Glutaraldehyde crosslinked, immunoprecipitated gulonolactone oxidase, injected intraperitoneally, has significant catalytic activity and is capable of providing long-term therapeutic benefit for the enzyme deficiency disease scurvy. The enzyme is tolerated even in repetitive doses. In the present study, however, we have found that when administered intra-arterially this modified enzyme is quite toxic even in single doses. Prior to administration the enzyme complex was filtered through a 5-microns filter. When administered intravascularly the enzyme is not nearly as active catalytically. In spite of this, activity can be detected in vivo as an elevation of plasma ascorbic acid and prolonged survival of guinea pigs fed without the vitamin. Following administration both activity and the enzyme complex are rapidly removed from the circulation. Liver and spleen are largely responsible for this uptake. Because of its toxicity intra-arterial injection of this form of the enzyme does not appear suitable for enzyme therapy.
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001205:Ascorbic Acid / Q000097:blood; D001215:Asparaginase / Q000276:immunology; D002645:Chickens; D004355:Drug Stability; D006168:Guinea Pigs; D007106:Immune Sera; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D050544:L-Gulonolactone Oxidase; D008297:Male; D008861:Microsomes / Q000201:enzymology; D013401:Sugar Alcohol Dehydrogenases / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000936:Antigen-Antibody Complex; D007106:Immune Sera; D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; D001215:Asparaginase; D001205:Ascorbic Acid