The pathogenesis and toxicokinetics of locoweed (Astragalus and Oxytropis spp.) poisoning in livestock.

Locoweed poisoning is a chronic disease that develops in livestock grazing for several weeks on certain Astragalus and Oxytropis spp. that contain the locoweed toxin, swainsonine. The purpose of this review is to present recent research on swainsonine toxicokinetics and locoweed-induced clinical and histologic lesions. Swainsonine inhibits cellular mannosidases resulting in lysosomal storage disease similar to genetic mannosidosis. Diagnosis of clinical poisoning is generally made by documenting exposure, identifying the neurologic signs, and analyzing serum for alpha-mannosidase activity and swainsonine. All tissues of poisoned animals contained swainsonine, and the clearance rates from most tissues was about 20 hours (T1/2 half life). The liver and kidney had longer rate of about 60 hours (T1/2). This suggests that poisoned animals should be allowed a 28-day withdrawal to insure complete swainsonine clearance. Poisoning results in vacuolation of most tissues that is most obvious in neurons and epithelial cells. Most of these histologic lesions resolved shortly after poisoning is discontinued; however, some neurologic changes are irreversible and permanent.