Research Abstract

E36 - Susceptibility of Horses and Sheep to Hypoglycin A Intoxication: In/Ex Vivo Bioavailability and Cellular Effects

Friday, June 15
5:00 PM - 5:15 PM
Location: WSCC 615

Atypical myopathy / seasonal pasture myopathy is a toxic rhabdomyolysis of horses linked to the ingestion of hypoglycin A (HGA) contained in seeds and seedlings of some Acer tree species. Although the toxic effect of HGA’s metabolite, methylenecyclopropylacetic acid (MCPA), has been studied in several species, it remains unclear why animals (such as ruminants) that graze similar pastures to horses, appear unaffected. The objective of this study was to investigate the hypothesis that apparent low susceptibility in sheep is due to either low bioavailability of HGA or to HGA degradation in ruminal fluid, or to relative increased MCPA sensitivity of horse muscle.
HGA concentration was measured by a validated liquid chromatography-mass spectrometry method in serum samples from clinically healthy ewes (n=10) and horses (n=11) grazing on sycamore seedling-contaminated pastures. Additionally, sycamore seed homogenates were incubated with equine gastric fluid (n=6) and sheep ruminal fluid (n=5) samples for 1 hour and extracts assayed for HGA concentration. Finally, primary cells cultured from horse (n=4) and sheep (n=4) muscle samples were exposed to a range of MCPA concentrations for 24h and cytotoxic effects compared by MTT assay. Data were analysed using Mann-Whitney U or ANOVA tests.
Similar concentrations of HGA were detected in serum of clinically-unaffected sheep [range 5.2-125ng/ml] and horses [6.5-81.4 ng/ml] grazing contaminated pastures. There was no statistically significant difference in HGA concentration following sycamore seed homogenate incubation with either gastric or rumen fluid. Compared to sheep cells, horse cells had significantly higher in vitro compromise at MCPA concentrations between 4-6mM (p < 0.0001).
This study reveals that both sheep and horses absorb HGA following sycamore seedling ingestion and no evidence for HGA degradation after exposure to rumen fluid. Primary horse muscle-derived cells were more sensitive than sheep cells to the active HGA metabolite at low concentrations, suggesting greater muscle metabolic inhibition by MCPA in horses than in sheep. Though further study is necessary, this work potentially explains the apparent disparity in susceptibility to HGA intoxication between these species. 

Sonia Gonzalez-Medina, Ldo Vet, CertAVP(EM),CPOV, MRCVS

PhD student
Royal Veterinary college

After graduating in veterinary medicine at Cordoba University, Spain, I pursued a year of postgraduate equine training combining an internship in a referral equine hospital in Madrid (Spain) and two externships focusing on neonatology and medicine in the USA. After a short spell in equine first opinion in Spain, I did an internship at the Ecole Veterinaire d’Alfort in France and I moved to the UK in 2011 where I have worked in practice and at The Animal Health Trust while completing both a CertAVP (Equine Internal Medicine) and a Master in Veterinary oftalmology. I am currently finishing my PhD at the Royal veterinary College (London) in equine atypical myopathy, a disease that has fascinated me since undergraduate times.


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E36 - Susceptibility of Horses and Sheep to Hypoglycin A Intoxication: In/Ex Vivo Bioavailability and Cellular Effects


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