Contractile response of bovine lateral saphenous vein to ergotamine tartrate exposed to different concentrations of molecularly imprinted polymers

Authors: KUDUPOJE, MANOJ - UNIVERSITY OF KENTUCKY; Klotz, James; YIANNIKOURIS, ALEX - ALLTECH, INC.; DAWSON, KARL - ALLTECH, INC.; MCLEOD, KYLE - UNIVERSITY OF KENTUCKY; VANZANT, ERIC - UNIVERSITY OF KENTUCKY

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/26/2018
Publication Date: 1/20/2018
Citation: Kudupoje, M.B., Klotz, J.L., Yiannikouris, A., Dawson, K.A., McLeod, K.R., Vanzant, E.S. 2018. Contractile response of bovine lateral saphenous vein to ergotamine tartrate exposed to different concentrations of molecularly imprinted polymers. Toxins. 10(2):58. https://doi:10.3390/toxins10020058.
DOI: https://doi.org/10.3390/toxins10020058

Interpretive Summary: Ergot alkaloids produced by the fungal endophyte found in tall fescue are the toxins responsible for causing fescue toxicosis in grazing livestock. One strategy to mitigate or limit the effects of these toxins on livestock is to supplement with an adsorbent that prevents the absorption of the toxins from the digestive tract. Ergotamine, along with other ergot alkaloids, can influence vascular smooth contraction of bovine lateral saphenous veins. The objective of the current study was to evaluate the ergotamine binding activities of non-imprinted and molecularly imprinted polymers with a lateral saphenous vein bioassay to assess the effectiveness of the polymers. This study indicated that an incubation with either polymer reduced the contractile response to ergotamine in lateral saphenous veins in a dose dependent fashion with little evidence of differences between polymer type. However, further animal studies are required to assess the application of imprinted polymers as selective adsorbents of ergot alkaloids in feed. These findings will benefit research in support of the goal to mitigate fescue toxicosis with the validation of a polymer product that could be supplied in animal feed or mineral and ultimately benefit producers.

Technical Abstract: Ergot alkaloids, in their active isomeric form, affect animal health and performance and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted: MIP and non-imprinted: NIP polymers) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for 4 independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/NIP comparison. Norepinephrine normalized % contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log EC50 (-log [ETA]) of 6.59±0.26M). Although sample preparation time affected contractile response (P <0.001), pre-myograph incubation temperature (39 vs 21 °C, 1h) had no effect (P > 0.05). Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg-1 and affinity between 0.51 to 0.57 mg (R2: 0.83-0.92) for both polymers, with no difference between polymers (P >0.05). No difference (P = 0.62) in maximum inhibitory and IC50 response between MIP and NIP was noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2=0.87, P<0.01), for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids with little evidence of differences between MIP and NIP.