Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy

• Published in: Animals (Basel) Vol. 13; no. 15; p. 2410
• Main Authors: Sander, Johannes, Terhardt, Michael, Janzen, Nils, Renaud, Benoît, Kruse, Caroline-Julia, François, Anne-Christine, Wouters, Clovis P, Boemer, François, Votion, Dominique-Marie
• Format: Journal Article Web Resource
• Language: English
• Published: Switzerland MDPI AG 26.07.2023; Multidisciplinary Digital Publishing Institute (MDPI); MDPI
• Subjects: Acylcarnitines; Amino acids; Animal Science and Zoology; Animals; Atypical myopathy; Cerebrospinal fluid; Chromatography; Dehydrogenases; Enzymes; equine atypical myopathy; Euthanasia; General Veterinary; Horses; Hyperglycemia; Hypoglycin A; Hypoglycine A; Intoxication; Ions; Life sciences; Liver; Metabolism; Metabolites; methylenecyclopropylacetate; Mitochondria; Médecine vétérinaire & santé animale; Pancreas; Sapindaceae; Sapindaceae toxin; Sciences du vivant; Toxins; Veterinary (all); Veterinary medicine & animal health; Germany; methylenecyclopropylacetate; Sapindaceae toxin; equine atypical myopathy; acylcarnitines; hypoglycin A
• ISSN: 2076-2615; 2076-2615
• DOI: 10.3390/ani13152410

Equine atypical myopathy is caused by hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG), the known protoxins of sycamore maple ( ). 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.