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Fescue Toxicity in Sheep: I University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 12-1990 Fescue Toxicity in Sheep: I. Effects of Acremonium coenophailum on Total Splanchnic and Peripheral Flux of Energy Metabolites and Their Regulatory Hormones in Sheep. II. Hepatic Mixed- Function Oxidase Activity of Sheep Fed Fungus-Infested Fescue, Ergotamine Tartrate, Cimetidine and Metoclopramide Kenneth Patrick Zanzalari University of Tennessee, Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Animal Sciences Commons Recommended Citation Zanzalari, Kenneth Patrick, "Fescue Toxicity in Sheep: I. Effects of Acremonium coenophailum on Total Splanchnic and Peripheral Flux of Energy Metabolites and Their Regulatory Hormones in Sheep. II. Hepatic Mixed-Function Oxidase Activity of Sheep Fed Fungus-Infested Fescue, Ergotamine Tartrate, Cimetidine and Metoclopramide. " PhD diss., University of Tennessee, 1990. https://trace.tennessee.edu/utk_graddiss/4377 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Kenneth Patrick Zanzalari entitled "Fescue Toxicity in Sheep: I. Effects of Acremonium coenophailum on Total Splanchnic and Peripheral Flux of Energy Metabolites and Their Regulatory Hormones in Sheep. II. Hepatic Mixed-Function Oxidase Activity of Sheep Fed Fungus-Infested Fescue, Ergotamine Tartrate, Cimetidine and Metoclopramide." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Animal Science. Richard N. Heitmann, Major Professor We have read this dissertation and recommend its acceptance: James K. Miller, Karl M. Barth, John C. Waller, Dileep S. Sachan Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) To the Graduate Council: I am submitting herewith a dissertation written by Kenneth Patrick Zanzalari entitiled "Fescue toxicity in sheep: I. Effects of Acremonium coenophailum on total splanchnic and peripheral flux of energy metabolites and their regulatory hormones in sheep. II. Hepatic mixed-function oxidase activity of sheep fed fungus-infested fescue, ergotamine tartrate, cimetidine and metoclopramide." I have examined the final copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Animal Science. Dr. Richard N. Heitmann, Major Professor We have read this dissertation and recommend its acceptance: Dr.{IJ mes K. Miller # a_,tf1ttt. fl,� Dr. Karl M. BartW c ?7ufZ f': G Jf!i� Accepted for the Council: Vice Provost and Dean of The Graduate School FESCUE TOXICITY IN SHEEP I. EFFECTS OF ACREMONIUM COENOPHIALUM ON TOTAL SPLANCHNIC AND PERIPHERAL FLUX OF ENERGY METABOLITES AND THEIR REGULATORY HORMONES OF SHEEP II. HEPATIC MIXED-FUNCTION OXIDASE ACTIVITY OF SHEEP FED FUNGUS-INFESTED FESCUE, ERGOTAMINE TARTRATE, CIMETIDINE AND METOCLOPRAMIDE A Dissertation Presented for the Doctor of Philosophy Degree The University of Tennessee, Knoxville Kenneth Patrick Zanzalari December 19 90 ii DEDICATION To my wife Susan Delboy Zanzalari, whose assistance, patience, understanding, and most of all love, made completion of my doctorate degree a reality. iii ACKNOWLEDGEMENTS The author wishes to express his sincere gratitude to the following: To the Department of Animal Science at The University of Tennessee, Knoxville, for the opportunity to pursue this Doctorate Degree. To Dr. Richard N. Heitmann, major professor, whose unsurpassed knowledge, dedication, advise and guidance made pursuing this doctorate degree intellectually stimulating, educational and most of all enjoyable. His friendship throughout my graduate career was very much appreciated and will be missed upon graduation. To Dr. James K. Miller, major professor while pursuing a Masters' Degree, for serving on the graduate committee and for his friendship and assistance throughout my graduate program. To Dr. Karl M. Barth, "fellow DVC aggie", for serving on the graduate committee and whose friendship, support and advise throughout my graduate career was greatly appreciated. To Dr. John C. Waller, for serving on the graduate committee and for his friendship and assistance during my doctoral program. iv To Dr. Dileep s. Sachan, for serving on the graduate committee and for his friendship and astute advise throughout my program and in preparation of this dissertation for publication. To my mother, Dorothea, and father, Robert, for their love, support, understanding and encouragement throughout my life. I love you both. To my entire family for their love and support which I greatly appreciate. To Byron Housewright and Jimmy Wells for all their assistance in collection and analysis of samples and most of all their friendship. To all the graduate students in the Animal Science Department, for their friendship, support and assistance. V ABSTRACT Mature ewes were equipped with catheters in the portal, hepatic, mesenteric and femoral veins and femoral artery. Blood flows were measured by infusing a 1. 5% solution of para-aminohippurate into the mesenteric vein at .764 ml/min. Net fluxes of metabolites were calculated by multiplying veno-arterial differences by tissue blood flows. Study 1. Twenty experiments were conducted on five ewes to determine the effects of fungus-infested fescue hay on energy nutrients and regulatory hormone net fluxes. Ten experiments were conducted for each a fungus-free and fungus-infested fescue hay diet. Fungus-infested hay decreased arterial concentrations of acetoacetate and B­ hydroxybutyrate by 15 and 30% due to a 24% decrease in alimentary ketogenesis. However, this was less than 2% of the total digestible energy intake. Alkaloids present in fungus-infested fescue may stimulate the energy wasteful hepatic mixed-function oxidase system and may explain the increased rectal temperatures and decreased weight gains in animals experiencing fescue toxicity because the entire energy change of the reaction must be dissipated as heat. Study 2. Respiration rates, rectal temperatures and mixed­ function oxidase activity as measued by hepatic antipyrine uptake was measured in three ewes to determine the effects vi of fungus-infestation and i.v. cimetidine (800 mg/d/ewe). Antipyrine, (.218% w/v) was infused into a mesenteric vein. Respiration rates, rectal temperatures and hepatic antipyrine uptakes increased following 11 d consumption of fungus-infested fescue, whereas 4 d treatment with cimetidine lowered these parameters back to control values. Study 3. The efficacy of oral cimetidine (1200 mg/d) to reverse the changes observed in ewes fed fungus-infested hay were investigated using five ewes. Oral cimetidine did not change rectal temperatures, however, it increased plasma prolactin and decreased hepatic antipyrine uptake in ewes fed fungus-infested fescue. Study 4. The efficacy of ergotamine tartrate to mimic fescue toxicity and metoclopramide to ameliorate these effects were investigated using four ewes. Fungus­ infestation and ergotamine tartrate decreased plasma prolactin 69 and 94% and increased hepatic antipyrine extraction. Metoclopramide increased plasma prolactin concentrations and decreased hepatic antipyrine extraction in ewes fed fungus-infested fescue and ergotamine tartrate. vii TABLE OF CONTENTS CHAPTER PAGE PART I. GENERAL INTRODUCTION AND OVERVIEW I. INTRODUCTION . 1 II. LITERATURE REVIEW .. .. .. .. .. .. .. 3 GRASS-FUNGUS RELATIONSHIP ................... 3 ALKALOIDS AND FESCUE TOXICITY ................ 4 FESCUE FOOT . 5 Role of Alkaloids in Fescue Foot .......... 8 SUMMER FESCUE TOXICOSIS ...................... 9 Effects on Rumen Fermentation .............. 9 Effects on Dry Matter Intake ............... 11 Effects on Respiration Rates ............... 11 Effects on Rectal Temperatures ............. 11 Effects on Weight Gains .................... 12 Effects on Serum Prolactin ................. 13 BIOTRANSFORMATION AND MIXED-FUNCTION OXIDASES 13 TECHNIQUES FOR MEASURING MIXED-FUNCTION OXIDASE ACTIVITY 15 INHIBITION OF MIXED-FUNCTION OXIDASE ACTIVITY .............. 21 Cimetidine . 21 Metoclopramide . 23 SUMMARY ...................................... 25 LITERATURE CITED ...................................... 27 viii CHAPTER PAGE PART II. ENERGY METABOLITE AND REGULATORY HORMONE CONCENTRATIONS AND FLUXES ACROSS SPLANCHNIC AND PERIPHERAL TISSUES OF SHEEP FED FUNGUS-INFESTED FESCUE HAY I . ABSTRACT • . • . • • • . • . • . • . • • • • • • • • • . • . • • • • • • • • 3 6 II. INTRODUCTION . .. .. .. .. .. .. .. .. .. 38 III. MATERIALS AND METHODS ......................... 40 ANIMAL CARE .. .. .. .. .. .. .. .. 41 EXPERIMENTAL HAYS .. .. .. .. .. .. .. .. 41 SURGICAL TECHNIQUE .. .. .. .. .. .. .. 41 EXPERIMENTAL PROCEDURES ..................... 47 CHEM I CAL METHODS .. .. .. .. .. .. .. .. 47 CALCULATIONS . • • . 4 8 STATISTICAL ANALYSES ........ ................ 50 IV. RESULTS . 51 V. DISCUSSION . 57 GLUCOSE • . • . • . • . • • • . • .
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