Submitted to: New Zealand Veterinary Journal
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/12/2005
Publication Date: 10/1/2005
Citation: Strickland, J.R., Custis, M., Ashley, A.K., Smith, L.L., Klotz, J.L., Krehbiel, C. 2005. Clearance of Para-Aminohippuric Acid in Wethers Consuming Locoweed. New Zealand Veterinary Journal. 53(5):288-292. Interpretive Summary: Oral exposure of wethers to swainsonine via locoweed resulting in subclinical intoxication did not have any perceptible effects on para-aminohippuric acid serum concentrations or any of the pharmacokinetic parameters evaluated. Thus, symptomatic tissue damage associated with swainsonine exposure as indicated by elevated levels of alkaline phosphatase and aspartate aminotransferase activities did not appear to have deleterious effects on the disposition of para-aminohippuric acid. As such, the use of para-aminohippuric acid as a measure of blood flow rates to aid in delineating effects of swainsonine on blood flow and nutrient flux through splanchnic tissues of ruminants appears to be an acceptable model. Characterization of swainsonine effects on splanchnic metabolism will aid in the development of management strategies to improve livestock tolerance of locoweed.
Technical Abstract: Para-aminohippuric acid (PAH) is a non-metabolizable indicator frequently used to measure rates of blood flow through splanchnic vasculature in studies quantifying net flux of nutrients. Prevalence of locoweed toxicity in the western United States has generated interest in effects of the causative agent swainsonine (SW) on nutrient flux through splanchnic tissues. Because SW ingestion causes deleterious effects on kidney tissue, it is unclear if renal clearance of PAH is compromised in animals exposed to a diet containing SW. To validate the use of PAH as a marker for measuring blood flow, the subacute effect of SW exposure on PAH clearance in wethers consuming a mixed diet of locoweed and blue grama hay was evaluated. Fourteen sheep (60.1 + 6.4 kg) stratified by weight were assigned to one of three treatments: 1) 0.8 mg SW/kg BW (HI), 2) 0.2 mg SW/kg BW (LO), and 3) 0.0 mg SW/kg BW (CONTROL). To deliver the SW treatments, sheep were fed various ratios of locoweed and blue grama hay for 28 d prior to PAH infusion. To confirm SW exposure and subclinical intoxication, serum levels of SW, alkaline phosphatase (Alk-P) and aspartate aminotransferase (AST) were measured. A single injection of PAH was delivered (20 mL; 5% solution; pH = 7.4) into the jugular vein after subclinical intoxication had been achieved. Blood was drawn via jugular venipuncture immediately prior to PAH infusion and at timed intervals following the injection. Effective delivery of SW was evident through the significantly greater serum SW concentrations in HI compared to LO animals (P < 0.05). Subclinical SW intoxication was demonstrated through significantly greater activities of Alk-P and AST in LO and HI treatments compared to CONTROL animals (P < 0.05). No significant differences were detected for PAH rate of elimination (range = 0.097 to 0.108 L/min), elimination half-life (range = 6.62 to 7.24 min), apparent volume of distribution for the central compartment (range = 7.14 to 9.72 L), and clearance (range = 0.73 to 0.92 L/min) between treatments. These data indicate that subclinical SW intoxication does not affect the pharmacokinetics of PAH. Thus, use of downstream dilution of PAH has been determined to be a valid method to determine rate of blood flow in nutrient flux experiments that involve consumption of locoweed.