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Molecularly Imprinted Polymers Synthesized As Adsorbents for Ergot Alkaloids

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Molecularly Imprinted Polymers Synthesized As Adsorbents for Ergot Alkaloids University of Kentucky UKnowledge Theses and Dissertations--Animal and Food Sciences Animal and Food Sciences 2017 MOLECULARLY IMPRINTED POLYMERS SYNTHESIZED AS ADSORBENTS FOR ERGOT ALKALOIDS: CHARACTERIZATION AND IN VITRO AND EX VIVO ASSESSMENT OF EFFECTS ON ERGOT ALKALOID BIOAVAILABILITY Manoj B. Kudupoje University of Kentucky, [email protected] Author ORCID Identifier: https://orcid.org/0000-0002-5509-5559 Digital Object Identifier: https://doi.org/10.13023/ETD.2017.392 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Kudupoje, Manoj B., "MOLECULARLY IMPRINTED POLYMERS SYNTHESIZED AS ADSORBENTS FOR ERGOT ALKALOIDS: CHARACTERIZATION AND IN VITRO AND EX VIVO ASSESSMENT OF EFFECTS ON ERGOT ALKALOID BIOAVAILABILITY" (2017). Theses and Dissertations--Animal and Food Sciences. 76. https://uknowledge.uky.edu/animalsci_etds/76 This Doctoral Dissertation is brought to you for free and open access by the Animal and Food Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Animal and Food Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless an embargo applies. I retain all other ownership rights to the copyright of my work. I also retain the right to use in future works (such as articles or books) all or part of my work. I understand that I am free to register the copyright to my work. REVIEW, APPROVAL AND ACCEPTANCE The document mentioned above has been reviewed and accepted by the student’s advisor, on behalf of the advisory committee, and by the Director of Graduate Studies (DGS), on behalf of the program; we verify that this is the final, approved version of the student’s thesis including all changes required by the advisory committee. The undersigned agree to abide by the statements above. Manoj B. Kudupoje, Student Dr. Eric Vanzant, Major Professor Dr. D. L. Harmon, Director of Graduate Studies MOLECULARLY IMPRINTED POLYMERS SYNTHESIZED AS ADSORBENTS FOR ERGOT ALKALOIDS: CHARACTERIZATION AND IN VITRO AND EX VIVO ASSESSMENT OF EFFECTS ON ERGOT ALKALOID BIOAVAILABILITY DISSERTATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Agriculture, Food and Environment at the University of Kentucky By Manoj Bojappa Kudupoje Lexington, Kentucky Director: Dr. Eric Vanzant, Associate Professor of Animal and Food Sciences Lexington, Kentucky 2017 Copyright © Manoj Bojappa Kudupoje 2017 http://orcid.org/0000-0002-5509-5559 ABSTRACT OF DISSERTATION Alkaloid toxicities negatively impact livestock health and production and are of serious economic concern to animal industries. To date, few strategies have been developed to evaluate alkaloid levels in feed or to counteract alkaloid toxicities. The present research evaluated the applicability of imprinting technology to synthesize polymers that have potential to interact with ergot alkaloids and therefore reduce their bioavailability in the GIT. The studies also evaluated applicability of synthesized polymers for use in the ruminal environment using an in vitro ruminal fermentation model, and for the ability to ameliorate vasoconstriction using ex vivo myographic evaluations. In the first experiment, styrene-based molecularly imprinted polymer (MIP) was synthesized using ergotamine as the imprinting template and evaluated for specificity of adsorption to various ergot alkaloids. Cross reactivity with related alkaloids exists due to similarities in structure and functional groups. Both polymers (MIP and NIP) showed strong adsorption intensity and no difference was observed for estimated maximum adsorption capacity between MIP and NIP. Morphologically, MIP was highly porous with greater surface area than NIP. Solid phase extraction indicated stronger adsorption of MIP than NIP to ergot alkaloids suggesting the potential for MIP as a sorbent material for solid phase extraction (SPE) columns used for sample clean-up prior to HPLC or LC-MS/MS analysis of complex samples. In Experiment 2, methacrylic acid-based polymers were synthesized with ergotamine as a template. Among the 4 alkaloids evaluated for selectivity, adsorption difference between MIP and NIP interacted with alkaloid concentration, although differences were generally consistent across concentrations. Imprinting did not affect lysergol and bromocriptine adsorption, but resulted in higher adsorption to methylergonovine. However, there was no difference between MIP and NIP for adsorption of ergotamine. Hydrophobic interactions and H-bonding were the primary interactive forces between polymers and alkaloid adsorbents. Morphologically, MIP had greater surface area and porosity implying a larger surface for adsorption. In addition to its application as SPE sorbent, this MIP was a suitable candidate for application as a feed adsorbent to reduce the bioavailability of certain alkaloid in the gut. In experiment 3, methacrylic acid-based polymers were evaluated for their effect on in vitro ruminal fermentation. There were no interactions between polymer type and inclusion level, and no differences between polymer types for cumulative gas production or rate of gas production. Total gas production and rate of gas production were unaffected by inclusion level. Polymers did not affect total or individual VFA concentrations, ammonia-N or methane concentration at any inclusion level. However, a logarithmic increase in polymer dose level decreased the pH linearly with maximum depression of 0.24 units. This study indicated that, within the range of expected use levels, polymers were essentially inert and would not be expected to affect ruminal fermentation. In experiment 4, ex vivo myographic bioassays were used to determine the impact of polymers on ergotamine bioavailability. Responses measured in the ex vivo myographic studies had similar trend as the responses generated from in vitro isothermal adsorption studies. Results of that study also showed that ex vivo myographic responses could be predicted from in vitro isothermal adsorption studies with more than 80% accuracy. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity with little evidence of substantial differences between MIP and NIP. KEYWORDS: ergotamine, adsorbent, myograph, imprinted polymer, isotherms, fescue Manoj Kudupoje ---------------------------- Author’s Signature September 7, 2017 ---------------------------- Date MOLECULARLY IMPRINTED POLYMERS SYNTHESIZED AS ADSORBENTS FOR ERGOT ALKALOIDS: CHARACTERIZATION AND IN VITRO AND EX VIVO ASSESSMENT OF EFFECTS ON ERGOT ALKALOID BIOAVAILABILITY By Manoj Bojappa Kudupoje Dr. Eric Vanzant --------------------------------- Director of Dissertation Dr. D.L.Harmon --------------------------------------- Director of Graduate Studies September 7, 2017 -------------------------- Date This dissertation is dedicated to those who have supported and encouraged me throughout my life. My parents, Bojappa and Shanthy Kudupoje, who gave me the desire to never stop learning and taught me to follow my passions. My sister Mamatha and niece Apeksha, who reminded me to take a break now and then to see where my work and dreams met the real world. Friends too numerous to name, who kept me laughing and sane through it all. But, most of all, my wife Sandhya, who married into this wild ride and helped me with every step of my life. Without her I might still be working. I am grateful for your love and support. Most of all I dedicate everything to my kids, my daughter Aishanya and son Aayushman, who waited for me all these years, waiting eagerly to join them. ACKNOWLEDGMENTS First and foremost, I would like to express my deep sense of gratitude to my supervisor Prof. Dr. Eric Vanzant for giving me an opportunity to pursue a doctoral study in his group. I am very thankful to him for his, inspiring guidance, many discussions and resourceful ideas. He continuously supported me and let me guide my own research and make mistakes where it was acceptable. It was a good learning curve under his guidance during these years. He has laughed when things went wrong and pushed me to know more and work hard. I will forever be thankful for his guidance, support, and encouragement. I am thankful Dr. Lyons for the financial support from Alltech. My sincere gratitude towards Dr. Karl Dawson who saw potential in me and supported me through the Alltech- University of Kentucky Alliance program. I am also thankful to Dr. Alexandros Yiannikouris, my committee member, who initiated the topic of imprinting technology in animal industry for my PhD,
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