Ruminal Metabolism and Transport of Tall Fescue Ergot Alkaloids

Ayers, A. W.; Hill, Nicholas S.; Rottinghaus, George E.; Stuedemann, J. A.; Thompson, F. N.; Purinton, P. T.; Seman, Dwight H.; Dawe, Donald L.; Parks, A. H.; Ensley, Doug

doi:10.2135/cropsci2009.01.0018

Cited by 41 publications

(47 citation statements)

References 24 publications

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“…Total urinary EA concentration increased after 1 day of grazing, peaked on day 14, and remained elevated. The trend in urinary alkaloid excretion was consistent with previous studies (Ayers et al, 2009;Hill et al, 2000;Stuedemann et al, 1998), indicating animal's response to E+ grazing from this experiment is typical.…”

Section: Discussionsupporting

confidence: 91%

“…Rapid ergovaline metabolism and distribution to liver and kidney tissues also impedes its identification in the plasma (Ayers et al, 2009;De Lorme et al, 2007;Zbib et al, 2014). Besides using a broad, non-ergot alkaloid focused extraction method, some EA metabolites might not have been identified because of the lack of matching MS/MS spectra in existing reference metabolomics databases.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

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Metabolomics of fescue toxicosis in grazing beef steers

Mote

Hill

Uppal

et al. 2017

Food and Chemical Toxicology

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Fescue toxicosis (FT) results from consumption of tall fescue (Lolium arundinaceum) infected with an endophyte (Epichloë coenophiala) that produces ergot alkaloids (EA), which are considered key etiological agents of FT. Decreased weight gains, hormonal imbalance, circulating cholesterol disruption, and decreased volatile fatty acid absorption suggest toxic (E+) fescue-induced metabolic perturbations. Employing untargeted high-resolution metabolomics (HRM) to analyze E+ grazing-induced plasma and urine metabolome changes, fescue-naïve Angus steers were placed on E+ or non-toxic (Max-Q) fescue pastures and plasma and urine were sampled before, 1, 2, 14, and 28 days after pasture assignment. Plasma and urine catecholamines and urinary EA concentrations were also measured. In E+ steers, urinary EA appeared early and peaked at 14 days. 13,090 urinary and 20,908 plasma HRM features were detected; the most significant effects were observed earlier (2 days) in the urine and later (≥14 days) in the plasma. Alongside EA metabolite detection, tryptophan and lipid metabolism disruption were among the main consequences of E+ consumption. The E+ grazing-associated metabolic pathways and signatures described herein may accelerate development of novel early FT detection and treatment strategies.

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Section: Discussionsupporting

confidence: 91%

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Metabolomics of fescue toxicosis in grazing beef steers

Mote

Hill

Uppal

et al. 2017

Food and Chemical Toxicology

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“…If ergovaline is still being released as tissues turn over, then this will extend the time it takes for an animal to recover (as ergovaline is re-released) and clear ergovaline from their system. Alkaloid concentrations in ruminal fluid have been reported to decrease within 24 h of removal from endophyte-infected tall fescue pasture, and decrease to zero within 3 days after removal (Ayers et al 2009). Aiken et al (2011b) detected alkaloids (lysergyl) in urine collected from lambs still 4 days after switching them from an AR6 to an endophyte-free perennial ryegrass pasture, suggesting that the alkaloids are coming from a source other than rumen contents.…”

Section: Bioaccumulation and Excretion Of Ergovalinementioning

confidence: 99%

Ergovaline, an endophytic alkaloid. 1. Animal physiology and metabolism

Klotz

Nicol

2016

Anim. Prod. Sci.

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Abstract. Ergovaline is an ergot alkaloid found in some endophyte-infected ryegrasses and it has been implicated in the expression of ergotism-like symptoms of grazing livestock, as well as in the protection of the plant against invertebrate predation and abiotic stresses. These selection pressures have resulted in a conflict between the needs of the pasture for persistence and the needs of the animal for production. Ergovaline has not been well studied in terms of animal physiology until recently. There are several putative mechanisms that limit the bioavailability of ergovaline, ranging from microbial biotransformation to post-absorptive hepatic detoxification. Although there are mechanisms that protect the animal from ergovaline exposure, tissues are very sensitive to ergovaline, indicating that ergovaline is very potent and that small quantities have the potential to cause noticeable physiological effects. The range of physiological effects, including decreased circulating prolactin, vasoconstriction and increased susceptibility to heat stress are all linked to the interaction of ergovaline with biogenic amine receptors found throughout the body. This review will focus on understanding the variation of ergovaline concentration in terms of bioavailability, the myriad of hurdles a molecule of ergovaline must overcome to cause an effect, what the ergovaline-induced effects are in New Zealand livestock and how this relates to the potency of ergovaline.

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“…This is the first known report to show that ergovaline crosses the bovine rumen epithelium. Ayers et al (2009) showed that ergovaline did not cross bovine rumen epithelium isolated in a parabiotic chamber; however, the concentration used in their experiment may have resulted in serosal concentrations below the limit of detection. The estimation of flux rates presented here are significantly lower than those reported for ergotamine transport across ovine rumen and omasum tissue (Hill et al, 2001) as well as ergovaline movement across Caco-2 cells (Shappell and Smith, 2005).…”

mentioning

confidence: 91%

Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium

Foote

Penner

Walpole

et al. 2014

animal

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Ergot alkaloids in endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have been shown to cause a reduction in blood flow to the rumen epithelium as well as a decrease in volatile fatty acids (VFA) absorption from the washed rumen of steers. Previous data also indicates that incubating an extract of endophyte-infected tall fescue seed causes an increase in the amount of VFA absorbed per unit of blood flow, which could result from an alteration in the absorptive or barrier function of the rumen epithelium. An experiment was conducted to determine the acute effects of an endophyte-infected tall fescue seed extract (EXT) on total, passive or facilitated acetate and butyrate flux across the isolated bovine rumen as well as the barrier function measured by inulin flux and tissue conductance (G t ). Flux of ergovaline across the rumen epithelium was also evaluated. Rumen tissue from the caudal dorsal sac of Holstein steers ( n = 6), fed a common diet, was collected and isolated shortly after slaughter and mounted between two halves of Ussing chambers. In vitro treatments included vehicle control (80% methanol, 0.5% of total volume), Low EXT (50 ng ergovaline/ml) and High EXT (250 ng ergovaline/ml). Results indicate that there is no effect of acute exposure to ergot alkaloids on total, passive or facilitated flux of acetate or butyrate across the isolate bovine rumen epithelium ( P > 0.51). Inulin flux ( P = 0.16) and G t ( P > 0.17) were not affected by EXT treatment, indicating no alteration in barrier function due to acute ergot alkaloid exposure. Ergovaline was detected in the serosal buffer of the High EXT treatment indicating that the flux rate is~0.25 to 0.44 ng/cm 2 per hour. Data indicate that specific pathways for VFA absorption and barrier function of the rumen epithelium are not affected by acute exposure to ergot alkaloids from tall fescue at the concentrations tested. Ergovaline has the potential to be absorbed from the rumen of cattle that could contribute to reduced blood flow and motility and lead to reduced growth rates of cattle.Keywords: bovine, ergovaline absorption, fescue toxicosis, volatile fatty acid absorption ImplicationsResults from this experiment show that ergot alkaloids present in endophyte-infected tall fescue do not have an impact on nutrient absorption or barrier function of the isolated rumen epithelium of cattle following acute exposure. This indicates that previously observed reductions in nutrient absorption in live animals exposed to ergot alkaloids requires chronic exposure or is driven by the reduced blood flow. Results also show that ergovaline, one of the main causative agents of fescue toxicosis, is absorbed across the rumen epithelium, although it is at a fairly slow rate ∼1% of a daily dose.

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Ruminal Metabolism and Transport of Tall Fescue Ergot Alkaloids

Cited by 41 publications

References 24 publications

Metabolomics of fescue toxicosis in grazing beef steers

Metabolomics of fescue toxicosis in grazing beef steers

Ergovaline, an endophytic alkaloid. 1. Animal physiology and metabolism

Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium

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