Development of a toxin-binding agent as a treatment for tunicaminyluracil toxicity: protection against tunicamycin poisoning of sheep.

Abstract

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.

DESIGN:

Controlled treatment trial.

ANIMALS:

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

PROCEDURE:

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).

CONCLUSION:

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.

• Authors: C May, P L Stewart
• Journal: Australian veterinary journal (Aust Vet J) Vol. 76 Issue 11 Pg. 752-6 (Nov 1998) ISSN: 0005-0423 [Print] England
• PMID: 9862067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclodextrins
• beta-Cyclodextrins
• Tunicamycin
• betadex

Topics

• Animals
• Body Weight (drug effects)
• Cyclodextrins (chemistry, metabolism, therapeutic use)
• Disease Models, Animal
• Male
• Poisoning (drug therapy, veterinary)
• Sheep
• Sheep Diseases (chemically induced, drug therapy)
• Tunicamycin (metabolism, poisoning)
• beta-Cyclodextrins