Source: UNIVERSITY OF WYOMING submitted to NRP
TOXICITY OF XANTHOPARMELIA CHLOROCHROA IN RUMINANTS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0202718
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jan 1, 2005
Project End Date
Dec 31, 2006
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF WYOMING
1000 E UNIVERSITY AVE DEPARTMENT 3434
LARAMIE,WY 82071-2000
Performing Department
VETERINARY SCIENCES
Non Technical Summary
X. chlorochroa was responsible for a massive episode of elk mortality in 2004, however we have no idea why this ubiquitous plant "turned bad" at this particular time. The potential for a recurrence of the problem complicates forest and rangeland management in the northern Rockies. This project examines one possible lichen toxin as a prelude to identifying the toxin responsible for the Red Rim dieoff. The identity of the toxin is essential to future studies of the effects of environmental conditions, etc. on the toxicity lichen in the field.
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
1210710115010%
1213610115010%
1213899115010%
1350710115010%
1353899115020%
3140710115020%
3143610115010%
3143899115010%
Goals / Objectives
The overall objective of this project is to test the hypothesis that usnic acid causes muscle necrosis in ruminants, specifically sheep.
Project Methods
The hypothesis will be tested by completing the following specific objectives: 1. Develop a quantitative, sensitive method based upon GC/MS or LC/MS to measure usnic acid concentration in known toxic lichen. 2. Dose sheep with varying quantities of purified usnic acid based upon previous objective. 3. Monitor sheep for clinical signs of toxicity. 4. Monitor serum enzymes (clinical chemistry, CBC, etc.) for evidence of sub-clinical disease. 5. Examine (necropsy and histopathology) sheep for congruence of lesions with Red Rim elk. 6. Estimate the median lethal dose (LD50) and/or median toxic dose (ED50) for this species. 7. Bank sheep tissues for future studies of the condition.

Progress 01/01/05 to 12/31/06

Outputs
Yearling ewes were dosed with (+)-usnic acid in an attempt to replicate X. chlorochroa toxicity in elk. Doses up to 485 mg/kg body weight did not cause clinical signs, biochemical changes or morphologic lesions. Doses greater than 647 mg/kg were lethal within seven days. Intoxicated sheep exhibited only minimal clinical signs prior to dying, but had massive muscle necrosis at post mortem examination. There were no lesions attributable to usnic acid in other organ systems. It appears that usnic acid is not the toxic agent responsible for X. chlorochroa poisoning.

Impacts
We have ruled out usnic acid as the causative agent of X. chlorochroa poisoning.

Publications

  • Dailey, R. N., Raisbeck, M. F., Montgomery, D., Siemion, R. S., Ingram, J. S. (in prep) 2007. Usnic acid toxicity in sheep. J. Wildl. Dis.


Progress 01/01/05 to 12/31/05

Outputs
Ewes were fed increasing doses of usnic acid in a modified Brownlee up/down in an attempt to reproduce the syndrome seen in elk on the Red Rim during the winter of 2004. At approximately 400 mg/kg BW, feed refusal became apparent and the daily dose was administered together with 250 g of ground alfalfa via stomach tube, split into two doses bid for 7 days. Although no amount of usnic acid caused clinical signs similar to those seen in elk or in sheep fed lichen, doses of 785 mg/kg BW and 625 mg/kg BW caused sudden death 6 and 7 days, respectively, after dosing began. A dose of 480 mg/kg caused no clinical signs, clinicopathological abnormalities or morphologic lesions. Postmortem examination revealed extensive muscle necrosis of appendicular muscles, but none in cardiac, diaphragmatic or axial skeletal muscle. We conclude that the LD50 of usnic acid in ruminants is around 500 mg/kg. We also conclude that, while usnic acid may be 1 factor in X. chlorochroa toxicity, it is not the only toxin responsible for the syndrome of muscular weakness/paralysis seen in X. chlorochroa intoxication.

Impacts
Usnic acid and Xanthoparmelia lichens figure are used as nutriceuticals, even though there is virtually no information re: their toxicity in mammals. The species X. chlorochroa is also a very common feedstuff in western forests and rangelands. The fact that it is capable of causing massive mortalities in wildlife and livestock is still not completely accepted by many range managers. A better understanding of the toxicity of usnic acid and X. chlorochroa will facilitate rational management decisions in western rangelands.

Publications

  • Cook, W.E., Cornish, T.E., Williams, E.S., Brown, B., Hiatt, G., Kreeger, T.J. and Raisbeck, M.F. 2006. Xanthoparmelia chlorochroa intoxication in wapiti (Cervus canadensis). Poisonous Plants and Natural Toxins, CAB Int'l. In press.