Development of a toxin-binding agent as a treatment for tunicaminyluracil toxicity: protection against tunicamycin poisoning of sheep.
OBJECTIVE
To assess the ability of certain derivatives of beta-cyclodextrin to treat sheep affected by tunicaminyluracil toxicity, using tunicamycin poisoning as a model system.


METHODS
Controlled treatment trial.


METHODS
One hundred and sixty Merino wethers were used in the studies.


METHODS
Groups of sheep were experimentally poisoned with tunicamycin. Derivatives of beta-cyclodextrin, with or without magnesium sulphate and magnesium gluconate, were administered to treatment groups daily for 2 to 3 days. Treatment groups were compared with untreated groups in terms of survival.


RESULTS
A significant increase in survival was observed following treatment of tunicamycin-affected sheep with hydroxypropyl-beta-cyclodextrin (HP beta-CD) and magnesium sulphate in solution (P < 0.05). In subsequent trials, formulation of the cyclodextrin in the form of a magnesium gluconate gel suspension demonstrated significant protection (P < 0.01) and was equally as effective as the cyclodextrin in solution, but required half the frequency of administration, even when the treatment was not commenced until 24 h after the final toxin dose. Beta-cyclodextrin-epichlorohydrin copolymer also improved the survival rate. After toxin administration, the sheep lost significantly less weight if treatment with HP beta-CD was commenced early (P < 0.001).


CONCLUSIONS
Protection studies using these two beta-cyclodextrin derivatives suggest that they may be effective in increasing the survival of sheep poisoned by tunicamycin and warrant further testing in field outbreaks of annual ryegrass toxicity.
May
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Plant Toxins Unit, CSIRO Australian Animal Health Laboratory, Geelong, Victoria.
Stewart
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PL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003505:Cyclodextrins / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D011041:Poisoning / Q000188:drug therapy / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000139:chemically induced* / Q000188:drug therapy; D014415:Tunicamycin / Q000378:metabolism / Q000506:poisoning*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D014415:Tunicamycin; C031215:betadex