Hepatic Metabolism of Ergot Alkaloids in Beef Cattle by Cytochrome P450

Moubarak, Ali S.; Rosenkrans, C. F.

doi:10.1006/bbrc.2000.3210

Cited by 40 publications

(42 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A preliminary approach is presented, based on in vitro metabolism data and on LC-MS/MS selectivity, for the determination of relevant dihydroergotoxine metabolites for pharmacoki- The in vitro metabolism profiles depicted for the dihydroergotoxine components ( Figure 2) agree with previous observations on ergotamine [16] and DHEC [9]. Within 30 min of incubation two (a pair) more hydrophilic metabolites (M1/ M2, M4/M5, M7/M8) were produced from each of the dihydroergotoxine alkaloids assayed separately (Figure 2).…”

Section: Discussionsupporting

confidence: 78%

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results

Bicalho

Giolo

Lilla³

et al. 2007

Biopharm & Drug Disp

View full text Add to dashboard Cite

Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30 microM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27 mg) to a healthy volunteer (male, age 45, height 1.93 m, weight 103 kg). In this preliminary approach, the peaks (C(max)) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04 microg/l. The peaks (C(max)) of their hydroxy-metabolites were 0.98, 0.53 and 0.30 microg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma.

show abstract

Section: Discussionsupporting

confidence: 78%

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results

Bicalho

Giolo

Lilla³

et al. 2007

Biopharm & Drug Disp

View full text Add to dashboard Cite

show abstract

“…CYP3A has been shown to play a role in the inactivation of progesterone as well as in the clearance of ergot alkaloids from the body (Moubarak and Rosenkrans, 2000). The interaction of both progesterone and ergot alkaloids being cleared by similar enzymes could play a role in both the severity of the symptoms of fescue toxicosis as well as the circulating concentrations of progesterone.…”

Section: Discussionmentioning

confidence: 99%

Evaluating blood perfusion of the corpus luteum in beef cows during fescue toxicosis1

Cline¹,

Muth-Spurlock²,

Voelz³

et al. 2016

Journal of Animal Science

View full text Add to dashboard Cite

“…The first route is continuing on unabsorbed, with possible metabolism by hindgut microbes and eventual excretion via the faeces. The second route is absorption and vascular transport via the mesenteric veins to the liver through the portal circulation, for likely hepatic detoxification (Zanzalari et al 1989), most likely by cytochrome P450 (Moubarak and Rosenkrans 2000), or excretion via the biliary system back into the gut (Stuedemann et al 1998). A third route is an alternate path of absorption.…”

Section: Ergovaline Absorptionmentioning

confidence: 99%

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

Klotz

Nicol

2016

Anim. Prod. Sci.

View full text Add to dashboard Cite

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.

show abstract

Hepatic Metabolism of Ergot Alkaloids in Beef Cattle by Cytochrome P450

Cited by 40 publications

References 13 publications

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results

Evaluating blood perfusion of the corpus luteum in beef cows during fescue toxicosis1

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

Contact Info

Product

Resources

About