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      Ergot alkaloid mycotoxins: physiological effects, metabolism and distribution of the residual toxin in mice

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          Abstract

          The complex ergot alkaloids, ergovaline and ergotamine, cause dysregulation of physiological functions, characterised by vasoconstriction as well as thermoregulatory and cardiovascular effects in grazing livestock. To assess the effect of the mycotoxins, blood pressure and heart rate of male mice were measured, and metabolite profiling undertaken to determine relative abundances of both ergotamine and its metabolic products in body and brain tissue. Ergotamine showed similar cardiovascular effects to ergovaline, causing elevations in blood pressure and reduced heart rate. Bradycardia was preserved at low-levels of ergovaline despite no changes in blood pressure. Ergotamine was identified in kidney, liver and brainstem but not in other regions of the brain, which indicates region-specific effects of the toxin. The structural configuration of two biotransformation products of ergotamine were determined and identified in the liver and kidney, but not the brain. Thus, the dysregulation in respiratory, thermoregulatory, cardiac and vasomotor function, evoked by ergot alkaloids in animals observed in various studies, could be partially explained by dysfunction in the autonomic nervous system, located in the brainstem.

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          Bioactive alkaloids in vertically transmitted fungal endophytes

          Daniel G. Panaccione, Wesley T Beaulieu, Daniel P Cook … (2014)
          Article 0 comments Cited 48 times – based on 0 reviews     Review now
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            Ergovaline-induced vasoconstriction in an isolated bovine lateral saphenous vein bioassay.

            Paula L. Bush, Matthew Strickland, J. Klotz … (2007)
            Ergovaline has been proposed as a toxic component of endophyte-infected tall fescue. As many of the symptoms of fescue toxicosis are a result of compromised circulation, the objective of this study was to examine the vasoconstrictive potentials of ergovaline and a more documented ergopeptine, ergotamine, using a bovine, lateral (cranial branch) saphenous vein bioassay. Segments of the cranial branch of the lateral saphenous vein (2 to 3 cm) were collected from healthy, mixed breed cattle (n = 12 and n = 5 for the ergovaline and ergotamine experiments, respectively) at local abattoirs. The veins were trimmed of excess fat and connective tissue, sliced into 2- to 3-mm cross sections, and suspended in a myograph chamber containing 5 mL of a modified Krebs-Henseleit, oxygenated buffer (95% O2 + 5% CO2; pH = 7.4; 37 degrees C). The tissue was allowed to equilibrate at 1 g of tension for 90 min before of the addition of treatments. Increasing doses of ergovaline (1x10(-11) to 1 x10(-4) M) or ergotamine (1 x10(-11) to 1 x 10(-5) M) were administered every 15 min after buffer replacement. Contractile response data were normalized to a percentage induced by a reference dose of norepinephrine (1 x10(-4) M). Contractile responses of saphenous veins were similar for ergovaline and ergotamine. Initial contractile responses began at 1 x10(-8) M for both ergovaline and ergotamine (4.4 +/- 0.8% and 5.6 +/-1.1%, respectively). Vascular tension continued to increase as the alkaloid concentrations increased (maximums: 43.7 +/-7.1% at 1 x10(-5) M ergotamine; 69.6 +/- 5.3% at 1 x10(-4) M ergovaline). Interestingly, ergovaline-induced contractions (1 x10(-4) M) were not reversed by repeated buffer replacement over a 105-min period. As previously shown with ergotamine, these results confirm that ergovaline is a potent vasoconstrictor. The resistance of an ergovaline-induced contraction to relaxation over an extended period of time suggests a potential for bioaccumulation of this ergopeptine alkaloid and may aid in understanding its toxicity within the animal.
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              Biosynthesis of the ergot alkaloids.

              Nessa O’Connor, Dorota Jakubczyk, Johnathan Cheng (2014)
              The ergots are a structurally diverse group of alkaloids derived from tryptophan and dimethylallyl pyrophosphate (DMAPP) . The potent bioactivity of ergot alkaloids have resulted in their use in many applications throughout human history. In this highlight, we recap some of the history of the ergot alkaloids, along with a brief description of the classifications of the different ergot structures and producing organisms. Finally we describe what the advancements that have been made in understanding the biosynthetic pathways, both at the genomic and the biochemical levels. We note that several excellent review on the ergot alkaloids, including one by Wallwey and Li in Nat. Prod. Rep., have been published recently. We provide a brief overview of the ergot alkaloids, and highlight the advances in biosynthetic pathway elucidation that have been made since 2011 in Section 4.
              Article 0 comments Cited 29 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Priyanka Reddy: priyanka.reddy@agriculture.vic.gov.au
                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 16 June 2020
                Publication date PMC-release: 16 June 2020
                Publication date Collection: 2020
                Volume: 10
                Electronic Location Identifier: 9714
                Affiliations
                [1 ]ISNI 0000 0004 0407 2669, GRID grid.452283.a, Agriculture Victoria, AgriBio, Centre for AgriBioscience, ; Bundoora, Victoria 3083 Australia
                [2 ]ISNI 0000 0001 2342 0938, GRID grid.1018.8, School of Life Sciences, La Trobe University, ; Bundoora, Victoria 3083 Australia
                [3 ]ISNI 0000 0001 2342 0938, GRID grid.1018.8, School of Applied Systems Biology, La Trobe University, ; Bundoora, Victoria 3083 Australia
                Article
                Publisher ID: 66358
                DOI: 10.1038/s41598-020-66358-2
                PMC ID: 7298049
                PubMed ID: 32546814
                SO-VID: d1df773e-40a6-486d-9fc0-f482351254f5
                Copyright © © The Author(s) 2020
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 24 January 2020
                Date accepted : 15 May 2020
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Uncategorized
                Keywords: analytical biochemistry,mass spectrometry,biochemistry,diseases
                Data availability:
                ScienceOpen disciplines: Uncategorized
                Keywords: analytical biochemistry, mass spectrometry, biochemistry, diseases

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