TISSUE SWAINSONINE CLEARANCE IN SHEEP CHRONICALLY POISONED WITH LOCOWEED (OXYTROPIS SERICEA)

Locoweed poisoning is seen throughout the world and annually costs the livestock industry millions of dollars. Swainsonine inhibits lysosoma l alpha-mannosidase and Golgi mannosidase II. Poisoned animals are let hargic, anorexic, emaciated, and have neurologic signs that range from subtle apprehension to seizures. Swainsonine is water-soluble, rapidl y absorbed, and likely to be widely distributed in the tissues of pois oned animals. The purpose of this study was to quantify swainsonine in tissues of locoweed-poisoned sheep and determine the rate of swainson ine clearance from animal tissues. Twenty-four crossbred wethers were gavaged with ground Oxytropis sericea to obtain swainsonine doses of 1 mg swainsonine.kg(-1) BW.d(-1) for 30 d. After dosing, the sheep were killed on d 0, 1, 2, 3, 4, 6, 14, 30, 60, and 160. Animal weights and feed consumption were monitored. Serum was collected during dosing an d withdrawal periods, and tissues were collected at necropsy. Serum sw ainsonine concentrations were determined using an alpha-mannosidase in hibition assay. Swainsonine concentrations in skeletal muscle, heart, brain, and serum were similar at approximately 250 ng/g. Clearance fro m these tissues was also similar, with half-lives (T-1/2) of less than 20 h. Swainsonine at more than 2,000 ng/g, was detected in the liver, spleen, kidney, and pancreas. Clearance from liver, kidney, and pancr eas was about T-1/2 60 h. These findings imply that poisoned sheep hav e significant tissue swainsonine concentrations and animals exposed to locoweed should be withheld from slaughter for at least 25 d (10 T-1/ 2) to ensure that the locoweed toxin has cleared from animal tissues a nd products.