Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats

Authors: Davis, Thomas - Zane; Green, Benedict - Ben; Stegelmeier, Bryan; Lee, Stephen; Welch, Kevin; Pfister, James

Submitted to: Toxicon
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/16/2013
Publication Date: 12/15/2013
Citation: Davis, T.Z., Green, B.T., Stegelmeier, B.L., Lee, S.T., Welch, K.D., Pfister, J.A. 2013. Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats. Toxicon. 76:247-254.

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.

Technical Abstract: Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in the southwestern United States for many years; however, chemical composition of the plant as well as the dosage and duration required to cause toxicity have not been completely described. Tremetol, the historical toxin, is actually a mixture of alcohols and ketones. Though not completely confirmed experimentally, 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 of poisoning in Spanish goats and to document the pathophysiological changes associated with rayless goldenrod poisoning in goats. Goats dosed with rayless goldenrod containing 40 and 60 mg/kg of benzofurans for 4 or 5 days, showed clinical signs of toxicity that included trembles, and exercise intolerance seen as reluctance to perform on the treadmill, significantly increased resting and working heart rates and prolonged heart rate recovery following exercise. The affected goats also had significant serum biochemical changes 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, benzofuran ketones at doses at or above 40 mg/kg BW for longer than 4 or 5 days are toxic and produce disease similar to that described in clinical rayless goldenrod poisoning. The physiologic findings indicated that though there may be some myocardial changes, the majority of the clinical disease in goats is due to skeletal muscle degeneration and necrosis. More work is needed to determine the toxicity and physiologic effects of individual benzofuran ketones and to develop a model that better predicts the risk of poisoning and methods to avoid poisoning by benzofuran containing plants.