THE TOXICITY OF PYRROLIZIDINE ALKALOID-CONTAINING PLANTS AND OTHER HEPATOTOXIC AND NEUROTOXIC PLANTS
Location: Poisonous Plant Research
Title: Benzofuran ketone dosage-dependent rayless goldenrod (Isocoma pluriflora) toxicosis in a caprine model
Submitted to: American Journal of Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 19, 2011
Publication Date: N/A
Interpretive Summary: Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in the southwestern United States since the 1800s, however, the dosage and duration required to cause toxicity have not been defined. The toxic compound in rayless goldenrod was originally named tremetol. Tremetol is a mixture of alcohols and ketones and the toxic compounds are believed to be benzofuran ketones that include tremetone, dehydrotremetone, 3-hydroxytremetone, and 3-oxyangeloyl-tremetone. The objectives of this study were to determine the dosage of benzofuran ketones and the duration of exposure to these compounds required to produce clinical signs and the associated pathological changes of rayless goldenrod toxicosis in Spanish goats. Goats dosed with 40 and 60 mg/kg showed clinical signs of toxicity that included trembles, increased heart rates and prolonged recovery time following exercise. The affected goats also had significant changes in the serum that included increased concentrations of troponin I and increased activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. Exercise intolerant animals also had extensive degeneration and necrosis of nearly all skeletal muscles. In conclusion, we were able to produce benzofuran ketone dosage-dependent rayless goldenrod toxicosis in a caprine model. Additional research is underway to definitively identify the rayless goldenrod toxin or toxins and their pathogenic mechanism, as well as to develop models to provide prognostic information and formulate management protocols for poisoned animals.
The objectives of this study were to determine the dosage of benzofuran ketone compounds (tremetone, 3-hydroxytremetone, dehydrotremetone, and 3-oxyangeloyltremetone) and the duration of exposure to these compounds required to produce clinical signs and the associated pathological changes of rayles goldenrod toxicosis in Spanish goats. Twenty yearling female Spanish goats. Rayless Goldenrod (Isocoma pluriflora) was collected in the pre-flowering stage, dried, ground, and administered orally to goats at 0, 10, 20, 40, and 60 mg of benzofuran ketones/kg body weight/day for 7 days. Electrocardiograms were recorded daily before, during, and after exercising the goats on the treadmill. Serum was analyzed daily to monitor serum biochemical changes. The groups dosed with 40 and 60 mg benzofuran ketones per kg body weight developed severe clinical signs and had significant changes in resting heart rate, recovery time following exercise, and serum AST, ALT, LDH, and CK activities between days five and seven of the study. Three of the goats dosed with 10 or 20 mg benzofuran ketones per kg body weight showed minor changes on day seven of the study. The results of this study document for the first time the concentrations of tremetone, dehydrotremetone, and 3-oxyangeloyl-tremetone in rayless goldenrod that caused toxicity, as well as document that toxicity is dose dependent. This model will be used to determine the relative toxicities of the individual benzofuran ketone compounds as well as conduct studies to better understand rayless goldenrod toxicity.