Assessment of the vasoactive effects of the (S)-epimers of ergot alkaloids in vitro. (6th July 2020)

• Record Type: Journal Article
• Authors: Cherewyk, Jensen E; Parker, Sarah E; Blakley, Barry R; Al-Dissi, Ahmad N
• Is Part Of: Journal of animal science. Volume 98:Number 7(2020)
• Publication Date: 2020-07-06
• Subjects: bovine -- epimers -- ergot alkaloids -- metatarsal artery -- vasoconstriction; Livestock -- Periodicals; Livestock; Electronic journals; Periodicals; 636.005
• DOI: 10.1093/jas/skaa203
• Languages: English
• ISSNs: 0021-8812

Abstract

Abstract: Ergot alkaloids are produced by the fungus Claviceps purpurea and their levels are carefully monitored in animal and human diets due to their harmful effects and widespread contamination of cereal crops. Ergot alkaloids exist in two forms known as the ( R )- and ( S )-epimers with only the former being monitored in diets in North America. The ( S )-epimers of ergot alkaloids are thought to be biologically inactive and, therefore, harmless. A major mechanism by which the ( R )-epimers of ergot alkaloids produce their toxic effect is through vasoconstriction. Therefore, the objective of this study was to examine the vasoactivity potential (contractile response) of four ( S )-epimers, namely ergocryptinine, ergocristinine, ergocorninine, and ergotaminine utilizing an in vitro arterial tissue bath system. Bovine metatarsal arteries ( n = 6, ergocryptinine and ergocorninine; n = 6, ergocristinine and ergotaminine; n = 6 arteries/(S)-epimer, total n = 12) were collected from healthy mixed-breed beef steers immediately after slaughter, cut into 3-mm arterial cross sections, and suspended in a tissue bath with continuously oxygenated Krebs–Henseleit buffer. To assess the contractile response of each (S)-epimer, a cumulative contractile dose–response curve was constructed by incubating arteries with increasing concentrations (1 × 10 −11 to 1 × 10 −6 M) of that (S)-epimer. Contractile responses were recorded as grams of tension and were normalized to an initial contraction of phenylephrine. Contrary to the widespread belief, all tested ( S )-epimers were found vasoactive and produced a concentration-dependent arterial contractile response similar to what has been reported for the ( R )-epimers. The arterial contractile response to ergotaminine was strongest and was significantly greater than that of ergocryptinine and ergocristinine at the highest concentration used ( P ≤ 0.01). Our results indicate that the ( S )-epimers are biologically active and are likely harmful similar to the ( R )-epimers. The levels of ( S )-epimers should be carefully monitored in human and animal diets worldwide.