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United States Department of Agriculture

Agricultural Research Service

Research Project: OPTIMIZING THE BIOLOGY OF THE ANIMAL-PLANT INTERFACE FOR IMPROVED SUSTAINABILITY OF FORAGE-BASED ANIMAL ENTERPRISES

Location: Forage-Animal Production Research

Title: Bioaccumulation of Ergovaline in Bovine Lateral Saphenous Veins in Vitro

Authors
item Klotz, James
item Kirch, Brett
item Aiken, Glen
item Bush, Lowell - UNIVERSITY OF KENTUCKY
item Strickland, James

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 3, 2009
Publication Date: March 13, 2009
Citation: Klotz, J.L., Kirch, B.H., Aiken, G.E., Bush, L.P., Strickland, J.R. 2009. Bioaccumulation of Ergovaline in Bovine Lateral Saphenous Veins in Vitro. J Anim Sci. 2009. 87:2437-2447.

Interpretive Summary: Ergot alkaloids have been associated with vasoconstriction in grazing livestock afflicted with the fescue toxicosis syndrome. Previous in vitro investigations studying how ergot alkaloids cause the observed vasoconstriction have shown that ergovaline has a sustained contractile response. A similar contractile response has not been noted for lysergic acid. Using the bovine lateral saphenous vein bioassay, repetitive additions of 1x10-9 M ergovaline and 1x10-5 and 1x10-4 M lysergic acid resulted in contractile responses that did not increase with each addition. In contrast, the repetitive addition of 1x10-7 M ergovaline resulted in a contractile response that increased with each addition. Using mass spectrometry to measure alkaloid concentrations after the contractility experiments were completed, lysergic acid and ergovaline were detected at all 4 exposure levels (2x to 8x), but only the 1x10-7 M ergovaline treatment resulted in increased tissue content as the number of exposures increased. These data indicate that ergovaline, but not lysergic acid bioaccumulates with repetitive exposure in vitro. These results suggest that ergovaline may have a greater potential for inducing toxicosis in grazing animals than lysergic acid because of its potential to bioaccumulate at the cellular site of action.

Technical Abstract: Ergot alkaloids have been associated with vasoconstriction in grazing livestock afflicted with the fescue toxicosis syndrome. Previous in vitro investigations studying how ergot alkaloids cause the observed vasoconstriction have shown that ergovaline has a very distinct receptor affinity and sustained contractile response. A similar contractile response has not been noted for lysergic acid. The objectives of this study were to determine if repetitive in vitro exposure of bovine lateral saphenous vein to either lysergic acid or ergovaline would result in an increasing contractile response and if a measurable bioaccumulation of the alkaloids in the vascular tissue occurs over time. Segments of vein were either surgically biopsied from healthy cross-bred fescue-naïve yearling heifers (n = 16) or collected from healthy mixed breed and gender cattle immediately after slaughter (n = 12). Veins were trimmed of excess fat and connective tissue, sliced into cross-sections and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O2/5% CO2; pH = 7.4; 37oC). Contractile responses to repetitive additions of ergovaline (1x10-9 and 1x10-7 M) and lysergic acid (1x10-5 and 1x10-4 M) were evaluated using the biopsied veins. For the bioaccumulation experiments, veins collected at the abattoir underwent repetitive additions of 1x10-7 M ergovaline and 1x10-5 M lysergic acid and the segments were removed after every 2 additions and media rinses for alkaloid quantification via HPLC/MS. Contractile data were normalized as a percent of contractile response induced by a reference dose of norepinephrine (1x10-4 M). Repetitive additions of 1x10-9 M ergovaline and 1x10-5 and 1x10-4 M lysergic acid resulted in contractile response with a negative slope (P < 0.02). In contrast, repetitive addition of 1'10-7 M ergovaline resulted in a contractile response that increased with each addition (P < 0.01). Lysergic acid and ergovaline were detected at all 4 exposure levels (2x to 8x), but only the 1x10-7 M ergovaline treatment resulted in increased tissue content as the number of exposures increased (P < 0.05). These data indicate that ergovaline, but not lysergic acid bioaccumulates with repetitive exposure in vitro. These results suggest that ergovaline may have a greater potential for inducing toxicosis in grazing animals than lysergic acid because of its potential to bioaccumulate at the cellular site of action.

Last Modified: 9/2/2014
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