Toxicity of the Lichen Secondary Metabolite (+)-Usnic Acid in Domestic Sheep

Abstract

Abstract. Toxicity following ingestion of the vagrant, foliose lichen Xanthoparmelia chlorochroa was identified as the putative etiology in the death of an estimated 400-500 elk on the Red Rim-Daley Wildlife Habitat Management Area in Wyoming during the winter of 2004. A single, unsubstantiated report in 1939 attributed toxicity of X. chlorochroa in cattle and sheep to usnic acid, a common lichen secondary metabolite. To test the hypothesis that usnic acid is the proximate cause of death in animals poisoned by lichen, domestic sheep were dosed PO with (+)-usnic acid. Clinical signs in symptomatic ewes included lethargy, anorexia, and signs indicative of abdominal discomfort. Serum creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities were considerably elevated in symptomatic sheep. Similarly, only symptomatic ewes exhibited appreciable postmortem lesions consisting of severe degenerative appendicular skeletal myopathy. The median toxic dose (ED 50 ) of (+)-usnic acid in domestic sheep was estimated to be between 485 and 647 mg/kg/day for 7 days.

Review of Usnic Acid andUsnea BarbataToxicity

“…Other toxicity indices, such as serum lactate dehydrogenase, aspartate aminotransferase and creatine kinase, were also increased. A complete postmortem examination revealed that pathological changes occurred exclusively in the skeletal muscle (52). This is in sharp contrast with mice, rats, and humans, in which the liver is considered to be the most vulnerable organ with usnic acid insults.…”

“…Unfortunately, there was no further information regarding usnic acid-induced toxicity described in the report (51). Feeding domestic sheep with usnic acid of 323-776 mg/kg for a maximum of 9 days induced several clinical signs such as lethargy and anorexia, or even death, with the estimated median toxic dose between 485 and 647 mg/kg (52). Other toxicity indices, such as serum lactate dehydrogenase, aspartate aminotransferase and creatine kinase, were also increased.…”

“…This is in sharp contrast with mice, rats, and humans, in which the liver is considered to be the most vulnerable organ with usnic acid insults. Usnic acid is also the assumed toxicant and was associated with some 400-500 cow elk deaths occurred in Wyoming in 2004 (52,53). Necropsy revealed extensive muscle damage such as muscle pallor and streaking, particularly in the semitendinosus, semimebranous, and pelvic limbs.…”

Experimental Reproduction of Tumbleweed Shield Lichen (Xanthoparmelia Chlorochroa) Poisoning in a Domestic Sheep Model

“…Serum chemistries and a complete blood cell count were conducted on all blood samples, as previously described. 6 Urine was collected from each ewe at least once while the animal was on a 100% lichen diet via metabolism cage. Upon collection, urine samples were immediately filtered a and subsequently refrigerated until urinalysis (typically within 6-24 hr).…”

“…In a recent experimental study, however, administration of usnic acid orally did not duplicate the syndrome in domestic sheep. 6 Given the lack of information regarding X. chlorochroa toxicity, diagnosis is difficult, and treatment options are nonexistent. A combination of intravenous fluids; vitamins A, B, D, and E; selenium; calcium gluconate; dextrose phosphorus; magnesium; potassium; and anti-inflammatory and corticosteroid drugs had no beneficial effect in 4 symptomatic elk.…”