title: Use of 2,3,2-tetramine as a hepatic copper chelating agent for treatment of copper hepatotoxicosis in Bedlington terriers.
abstract: Five Bedlington Terriers with inherited copper (Cu) hepatotoxicosis and with hepatic Cu concentrations ranging from 3,000 to 11,000 micrograms/g of dry weight (normal, less than 350 micrograms/g of dry weight) were treated daily for up to 200 days with 2,3,2-tetramine tetrahydrochloride. During treatment, no change was made in the dietary Cu intake, which ranged from 12 to 16 micrograms/g of dry diet. Concentrations of hepatic and serum Cu, iron, and zinc were determined before and at the conclusion of the treatment period. In one dog, 24-hour urinary Cu concentration was measured before and during treatment. A liver biopsy specimen obtained after treatment had significantly (P less than 0.05) reduced hepatic Cu concentration (3,282 micrograms/g of dry weight; a 54.9% reduction), compared with the pretreatment value (7,281 micrograms/g of dry weight). After treatment, there was an overall general lessening of the extent of hepatic morphologic damage. Cytochemical examination for Cu in rhodanine-stained biopsy specimens revealed decreased numbers of Cu-laden hepatic lysosomes. The mean daily urinary Cu concentration increased as much as 25-fold during 2,3,2-tetramine treatment. Hepatic iron and zinc concentrations and serum Cu concentrations remained within normal ranges after treatment. Clinical or laboratory evidence of 2,3,2-tetramine toxicosis was not detected during treatment. These findings indicated that in affected Bedlington Terriers, 2,3,2-tetramine was a safe and rapid chelating agent of hepatic Cu.
authors.affiliation: Department of Clinical Sciences, Colorado State University, Fort Collins 80523.
authors.forename: D C
authors.initials: DC
authors.lastname: Twedt
authors.forename: H A
authors.initials: HA
authors.lastname: Hunsaker
authors.forename: K G
authors.initials: KG
authors.lastname: Allen
mesh_terms: D000818:Animals; D003300:Copper / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics; D004285:Dogs; D005029:Ethylenediamines / Q000627:therapeutic use*; D005260:Female; D007501:Iron / Q000032:analysis / Q000097:blood; D008099:Liver / Q000032:analysis / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D008297:Male; D008664:Metal Metabolism, Inborn Errors / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D010375:Pedigree; D014266:Trientine / Q000627:therapeutic use*; D015032:Zinc / Q000032:analysis / Q000097:blood
chemical_list: D005029:Ethylenediamines; D003300:Copper; D007501:Iron; D015032:Zinc; D014266:Trientine