Responsiveness of prehaemolytic copper poisoning in sheep from a specific pathogen-free environment to a relatively high dose of tetrathiomolybdate.
Efficacy of ammonium tetrathiomolybdate (3.4 mg/kg LW, TTM(3.4)) was monitored in nine, specific pathogen-free sheep with mild-to-severe, prehaemolytic copper poisoning (pre-HCP). Five sheep were given three subcutaneous injections over seven days and four began a shorter, five-day course four days later. Plasma bile acid (BA) and glutamate dehydrogenase (GDH) had fallen significantly after six days but BA briefly rose again between days 10 to 18. Aspartate aminotransferase (AST), δ-glutamyl transferase (GGT) were later to decline but presented little evidence of hepatotoxicity by day 45. Erythrocyte superoxide dismutase (ESOD) was rapidly inhibited, activities falling by 65 per cent within three days and taking 25 days to recover. Trichloroacetic (TCA)-insoluble copper increased by 6 to 8 μmol/l after three days but had largely disappeared by day 18. Six lambs had become hypercupraemic by day 18 due to a rise in TCA-soluble Cu. ESOD activity fell again by 188 ± 29.5 U/gHb between days 25 and 45 but had largely recovered by day 62. TTM(3.4) gave better control of hepatotoxicity than TTM(1.7) had done in more severely affects cohorts but at the expense of greater inhibition of ESOD. Treatment of pre-HCuP should rely more on reducing copper absorption until more is known of the side effects of TTM on cuproenzymes.
Moredun Foundation, Pentlands Science Park, Edinburgh EH26 0PZ, UK. suttle_hints@hotmail.com
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D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D003300:Copper / Q000097:blood / Q000506:poisoning*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004912:Erythrocytes / Q000201:enzymology; D008982:Molybdenum / Q000009:adverse effects / Q000627:therapeutic use*; D011897:Random Allocation; D012756:Sheep; D012757:Sheep Diseases / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D013047:Specific Pathogen-Free Organisms; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases