methylenecyclopropylacetate; Animal Science and Zoology; Veterinary (all); General Veterinary; Atypical myopathy; Acylcarnitines; Sapindaceae; Hypoglycine A; Hypoglycin A
Abstract :
[en] Equine atypical myopathy is caused by hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG), the known protoxins of sycamore maple (Acer pseudoplatanus). Various tissues from five atypical myopathy cases were analyzed but only HGA was found. Whether deamination of MCPrG has already occurred in the intestine as the first stage of metabolization has not been investigated. Activation of the protoxins to methylenecyclopropylacetyl (MCPA)-CoA and methylenecyclopropylformyl (MCPF)-CoA, respectively, occurred mainly in the skeletal muscles, as evidenced by very high concentrations of MCPA-carnitine and MCPF-carnitine in this tissue. Inhibition of the acyl-CoA dehydrogenases of short- and medium-chain as well as branched-chain fatty acids by the toxins led to a strong increase in the corresponding acylcarnitines, again preferentially in skeletal muscles. An accumulation of the long-chain acylcarnitines beyond the level of the control samples could not be detected in the tissues. As a high amount of HGA was always found unmetabolized in the organs, we speculate that targeting the interruption of further metabolization might be a way to stop the progression of intoxication. Inhibition of the mitochondrial branched-chain amino acid aminotransferase, i.e., the first enzyme responsible for the activation of sycamore maple protoxins, could be a therapeutic approach.
Sander, Johannes ; Screening-Labor Hannover, 30952 Ronnenberg, Germany ; Department of Clinical Chemistry, Hanover Medical School, 30625 Hanover, Germany
Terhardt, Michael ; Screening-Labor Hannover, 30952 Ronnenberg, Germany
Janzen, Nils ; Screening-Labor Hannover, 30952 Ronnenberg, Germany ; Department of Clinical Chemistry, Hanover Medical School, 30625 Hanover, Germany
Renaud, Benoît ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Kruse, Caroline ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Physiologie neuro-musculaire, de l'effort - Médecine sportive des animaux
François, Anne-Christine ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
Wouters, Clovis ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Boemer, François ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Votion, Dominique ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Language :
English
Title :
Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy.
Publication date :
26 July 2023
Journal title :
Animals
eISSN :
2076-2615
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
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