Evaluation of oral citrulline administration as a mitigation strategy for fescue toxicosis in sheep

Authors: GREENE, MASLYN - Clemson University; Klotz, James; GOODMAN, JACK - University Of Kentucky; MAY, JOHN - University Of Kentucky; Davis, Brittany; BALDWIN, WILLIAM - Clemson University; STRICKLAND, JAMES - Clemson University; BRITT, JESSI - Clemson University; SCHRICK, F. - University Of Tennessee; DUCKETT, SUSAN - Clemson University

Submitted to: Translational Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/23/2020
Publication Date: 10/30/2020
Citation: Greene, M.A., Klotz, J.L., Goodman, J.P., May, J.B., Harlow, B.E., Baldwin, W., Strickland, J.R., Britt, J.L., Schrick, F.N., Duckett, S.K. 2020. Evaluation of oral citrulline administration as a mitigation strategy for fescue toxicosis in sheep. Translational Animal Science. 4(4):txaa197. https://doi.org/10.1093/tas/txaa197.
DOI: https://doi.org/10.1093/tas/txaa197

Interpretive Summary: This study evaluated the potential for the supplementation of the amino acid citrulline to mitigate the negative effects of fescue toxicosis on pregnant ewes. We have previously demonstrated that there is severe intra-uterine growth restriction in ewes exposed to toxins found in tall fescue. This results in smaller malformed offspring. We have also shown that this is a consequence of decreased umbilical blood flow. Citrulline is an amino acid that can be cheaply fed that is metabolized by the ewe and can elevate a vasodilating substance, nitric oxide. Supplementation in this study did alter fetal growth, but the dose was not sufficient to produce a sustained circulating concentration in the ewe. Future research is being planned to further investigate this simple strategy for mitigation of fescue toxicosis. Presently, other researchers would be most interested in this research, but further work holds promise for a simple solution that could be incorporated into an animals drinking water and would have a large positive impact on the producer level.

Technical Abstract: Background: Gestating ewes consuming ergot alkaloids, from endophyte-infected (E+) tall fescue seed, produce smaller lambs suffering from intrauterine growth restriction. Arginine (Arg) supplementation has been shown to increase birth weight and oral citrulline (Cit) administration is reported to increase arginine concentrations. Two experiments were conducted to: 1) evaluate if oral supplementation with Cit or water, to ewes consuming E+ fescue seed, increases lamb birth weight and 2) determine the effectiveness of Cit and citrulline:malate as an oral drench in elevating circulating levels of Cit to determine dosing levels and frequency of dose. In Experiment 1, gestating Suffolk ewes (n = 10) were assigned to one of two treatments [oral drench of citrulline-malate 2:1 (CITM; 81 mg/kg/d of citrulline) or water (TOX)] to start on d 86 of gestation. In Experiment 2, non-pregnant Suffolk ewes (n = 3) were assigned to either oral citrulline (CIT; 81 mg/kg/d), citrulline-malate 2:1 (CITM; 81 mg/kg/d of citrulline), or water (CON) drench in a Latin Square design for a treatment period of 4 d with a washout period of 3 d. On d 4, blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 18 h post drench. Results: Expt 1: Ewes on CITM treatment had decreased (P < 0.05) plasma Arg and Cit concentrations during gestation. At birth, lambs from CITM ewes had reduced (P < 0.05) crude fat and total fat but did not differ (P > 0.05) in birth weight from lambs born to TOX ewes. Expt 2: Oral drenching of CIT and CITM increased (P < 0.0001) Cit concentrations within 2 h and levels remained elevated for 8 h. Apparent half-life of elimination for CIT and CITM were 8.484 h and 10.392 h respectively. Conclusions: Our results show that lamb birth weight was not altered with a single oral drench of citrulline-malate; however, lamb body composition was altered. The level and frequency of citrulline dosing may need to be greater in order to observe consistent elevation of Cit/Arg concentrations to determine its effectiveness in mitigating fescue toxicosis.