Submitted to: New Zealand Veterinary Journal
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/13/2005
Publication Date: 2/1/2006
Citation: Strickland, J.R., Ashley, A.K., Custis, M., Ashley, R. 2006. Toxicokinetic profile of swainsonine following exposure to locoweed (Oxytropis sericea)in naive and previously-exposed sheep. New Zealand Veterinary Journal. 54(1):34-40. Interpretive Summary: This research indicates that multiple compartments are likely involved in swainsonine disposition in ruminants. Given that dosage and previous exposure to swainsonine alter its own toxicokinetic profile, dosage and length of exposure effects warrant further attention in future research efforts. Additional research is needed to fully elucidate the toxicokinetic profile. This would include exploration of the possibility of that swainsonine is metabolized, sequestrated in tissue, bound by blood protein, and/or is reabsorbed following excretion. Should the true elimination half-lives prove to be as high as ~95 hours shown for the 0.4 mg swainsonine/kg body weight treatment in Trial 1, then clearing the compound (~10 half-lives) from sheep would require approximately 40 days. Therefore, producers must recognize that potentially long periods of withdrawal from locoweed-infested pastures prior to shipping animals for slaughter or finishing may be required to avoid added stress on the animals.
Technical Abstract: Toxicokinetic profiles of swainsonine (SW) following acute and subacute exposure were investigated. Twenty-nine wethers were stratified by BW (68.0 + 7.6 kg) and randomly assigned to one of five treatments. Treatments were: 0 (n=5), 0.4 (n=5), and 1.6 (n=5) mg SW/kg BW for Trial 1 and 0 (n=4), 0.2 (n=5), and 0.8 (n=5) mg SW/kg BW for Trial 2. Acute exposure in both trials included adaptation to blue grama (14 d) with no previous locoweed (i.e., swainsonine) exposure. Subacute exposure was defined by ingestion of blue grama and locoweed (428 'g SW/g locoweed) diet for 21 d in Trial 1 and 26 d in Trial 2 with subsequent removal from locoweed for 5 d prior to oral exposure to SW. For intensive sampling periods, SW was delivered via oral administration of a locoweed extract immediately following 0 h sampling. Blood samples were collected via jugular venapuncture twice daily for 3 d prior to initial SW exposure and then every 7 d for monitoring for subclinical intoxication by serum enzyme analysis (alkaline phosphatase, Alk-P; aspartate aminotransferase, AST). Serum SW time level curves were constructed from analysis of serum collected every h for 0-12 h, every 3 h for 15-24 h, every 6 h for 30-48 h, and every 12 h for 60-168 h. Serum SW levels were determined using the '-mannosidase inhibition assay (detection limit = 25 ng/mL). Elevated (P < 0.05) serum Alk-P and AST activities indicated that subclinical intoxication was induced by SW during subacute exposure for both trials. Additionally, serum SW was detected in all animals consuming locoweed during subacute exposure for both trials. Calculated rates of elimination were faster (P < 0.001) for 1.6 versus 0.4 (Trial 1) and 0.8 versus 0.2 (Trial 2) mg SW/kg BW. Rates of elimination indicated that SW was removed from serum faster (P < 0.06) following acute exposure than subacute exposure in both trials. Higher exposure rates to SW resulted in higher serum SW activities within trial. Serum SW time-level plots indicate that multiple compartments are involved in SW kinetics. Data indicate that dose and previous exposure alter SW toxicokinetics. Additional research using more sensitive measures of serum SW detection is warranted before definitive recommendations on SW exposure and withdrawal periods can be made.