Comparative study on the metabolism of the ergot alkaloids ergocristine, ergocryptine, ergotamine, and ergovaline in equine and human S9 fractions and equine liver preparations.

The research focuses on understanding metabolism of ergot alkaloids – ergocristine, ergocryptine, ergotamine, and ergovaline in horses compared to humans. This insight aids in conducting toxicological analysis of these drugs in urines or feces of afflicted horses.

Article Context

• This study is set in the backdrop of suspected association of Ergopeptine alkaloids like ergovaline and ergotamine with fescue toxicosis and ergotism in horses.
• There is a significant knowledge gap about metabolism of these ergot alkaloids, and this study was envisaged to address this gap with main focus on horses, but including humans for comparative analysis.

Research Methodology

• Reversed-phase liquid-chromatography coupled with high-resolution tandem mass spectrometry was used to analyse the alkaloid incubations with human and equine liver S9 fractions.
• Metabolite structures were hypothesized by comparing their MS spectra with the parent alkaloids.

Research Findings

• All the compounds were extensively metabolized yielding nor-, -oxide, hydroxy and dihydro-diole metabolites with majority patterns being common for both equine and human liver S9 fractions.
• Certain metabolic steps were unique to human metabolism like the formation of 8′-hydroxy metabolites, whereas the formation of 13/14-hydroxy and 13,14-dihydro-diol metabolites were unique to horse metabolism.
• A lesser number of metabolites were yielded when equine whole liver preparations were used for the incubations as compared to S9 fractions.

Research Application

• The findings can help in developing metabolite-based screenings for these alkaloids, thus allowing for a longer detection window in urine or feces samples from affected horses.