STUDIES ON THE TOXIC PRINCIPLE OF Asclepias eriocarpa AND Asclepias labriformis

Abstract

Some milkweeds native to the western United States are extremely toxic to range animals. As little as 0.8 ounce of Asclepias labriformis and 4 ounces of Asclepias eriocarpa, for example, can be lethal to a 100 pound sheep. The cardiac glycosides (cardenolides) in these species have been implicated as toxic principles. Experiments were conducted to verify this, and to determine the toxicity of three individual cardenolides common to both plant species. Four preparations were tested: dried, ground A. labriformis and A. eriocarpa plants, an ethanolic A. eriocarpa extract, and an extract from which pigments and fats had been removed. In addition, a purified cardenolide present in A. labriformis and A. eriocarpa, labriformin, and digitoxin, a clinically important cardenolide, were administered. Toxic symptoms and gross and histopathologic lesions were qualitatively similar in sheep regardless of whether plants, extracts, labriformin, or digitoxin were administered. Three cardenolides, labriformin, labriformidin, and eriocarpin, have been isolated from A. labriformis and A. eriocarpa and chemically characterized. They represent a new series of cardenolides similar, but not identical to those present in A. curassavica, a species whose cardenolides have undergone some toxicological investigation. Acute toxicity studies on these A. labriformis and A. eriocarpa cardenolides and uscharidin and calotropin from A. curassavica were performed using male Swiss Webster mice. Each LDSO is below 15 mg/kg. These cardenolides were also assayed for their ability to inhibit Na+−K+-ATPase, the proposed pharmacological receptor for cardiac glycosides in the heart. The milkweed cardenolides were comparable to ouabain in ability to inhibit lamb heart ATPase in vitro. Cardiac glycosides present in A. eriocarpa and A. labriformis represent a highly toxic group of compounds that account for the effects of these plants on sheep.