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Title: Physiologic effects of ergot alkaloids: What happens when excretion does not equal consumption?

item Klotz, James

Submitted to: Journal of Animal Science
Publication Type: Review Article
Publication Acceptance Date: 7/9/2015
Publication Date: 12/1/2015
Citation: Klotz, J.L. 2015. Physiologic effects of ergot alkaloids: What happens when excretion does not equal consumption? Journal of Animal Science. 93:5512-5521.

Interpretive Summary: The relationship between ergot alkaloids and livestock is not fully defined. There remains a dearth of available data that mechanistically describes the interaction of ergot alkaloid biologic systems in a manner that fully explains observed symptoms. What causes the variation in the observed response to ergot alkaloid exposure from animal to animal? There are still several areas from the release of an alkaloid from an ingested feedstuff to excretion that could result in variable responses observed in livestock. These range from microbial interactions, hepatic metabolism, various excretory routes, and the potential for a tissue residence time that persists after removal from the source of ergot alkaloids. This review outlines these areas as possible explanations for the variable responses to ergot alkaloid exposure in ruminants and exposes critical areas where further research is required to fully understand the ergot alkaloid and forage-animal interaction.

Technical Abstract: Increased persistence of tall fescue (Lolium arundinaceum) infested with an endophytic fungus Epichloë coenophiala (formerly Neotyphodium coenophialum) in forage-based agriculture has led to increased effort in understanding the negative effects caused by consumption of ergot alkaloids by animals consuming this forage. Ergot alkaloids have been shown to have an extremely short plasma half-life, but this does not necessarily equate to total clearance. Studies that measured alkaloids consumed and excreted have demonstrated that, in the case of ergovaline, less is excreted than is consumed. The fate of ergot alkaloids that leave circulation, but are not excreted, is not well understood. Consequently, these ‘alkaloid balance studies’ have led to speculation that ergovaline might bioaccumulate in the animal. Unfortunately, there are little data that indisputably support this outcome. Progress has been slowed by the fact that the fungus produces a multitude of different ergot alkaloids that can bind to a variety of different receptors. Multiple in vitro studies have shown that ergopeptine alkaloids (like ergovaline) have a persistent receptor-binding effect that results in a sustained contractile response and the consequence is the vasoconstriction associated with fescue toxicosis. If binding affinities of ergot alkaloids like ergovaline are sufficient to permit a post-absorptive accumulation, then a gradual build up may occur through chronic exposure to ergot alkaloids achieved by grazing. In vitro analyses have revealed a potential for vascular accumulation of ergot alkaloids through repetitive exposures to low concentrations. Interestingly, cattle exposed to ergot alkaloids in vivo have a consistently lower vascular response to agonists that target receptors known to bind ergot alkaloids. If these same receptors are blocked with an antagonist, contractile response to ergopeptine alkaloids is also reduced significantly (>60% reduction). This observation that alkaloid exposure interrupts normal function of a receptor can persist 5 to 6 weeks after animals have been removed from an ergot alkaloid source (and prolactin levels have long since returned to normal). Thus, clearance of ergot alkaloids from cattle that were grazing pasture with ergot alkaloid-producing endophytes may occur in a similar gradual manner. Studies that improve the understanding of how cattle process ergot alkaloids will help answer the question of whether ergot alkaloids bioaccumulate