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Home / Equine Research Bank / Animals (Basel) / Tissue Specific Distribution and Activation of Sapindaceae T...
Animals : an open access journal from MDPI2023; 13(15); doi: 10.3390/ani13152410

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

Abstract: 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.
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Publication Date: 2023-07-26 PubMed ID: 37570219PubMed Central: PMC10417358DOI: 10.3390/ani13152410Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the specific locations and activation methods of toxins from the Sapindaceae family in horses suffering from Atypical Myopathy. It suggests that preventing further metabolization of the toxin Hypoglycin A could potentially halt the disease’s progression.

Details of the Research

  • The research began by identifying the cause of Equine Atypical Myopathy, a disease in horses. Two toxic substances called Hypoglycin A (HGA) and Methylenecyclopropylglycine (MCPrG) found in the sycamore maple tree were found to be responsible for this disease.
  • The paper then explores the tissue distribution and activation of these toxins in five cases of Atypical Myopathy in horses. Of the two toxins, only HGA was found in the various tissues analyzed. However, it was not clearly identified whether MCPrG had already undergone a process called deamination in the intestine, which is the first step of metabolization.

Activation of Protoxins

  • The researchers found that the activation of the identified protoxins into their toxic forms (Methylenecyclopropylacetyl (MCPA)-CoA and Methylenecyclopropylformyl (MCPF)-CoA) mainly occurred in the skeletal muscles. This was determined by the high concentrations of their metabolites (MCPA-carnitine and MCPF-carnitine) found in this tissue.
  • These toxins were found to interfere (inhibit) with enzymes called acyl-CoA dehydrogenases, which are vital in the metabolism of certain types of fatty acids. This inhibition resulted in an increase of the corresponding acylcarnitines, with the skeletal muscles being most affected. However, an accumulation of these acylcarnitines wasn’t observed in the tissue samples when compared with healthy control samples.

Interruption of Toxin Metabolization

  • The study uncovered that a large amount of HGA remains unmetabolized in the organs of the affected horses. This lead to the hypothesis that hindering the metabolization process of this toxin could halt the progression of the disease.
  • The paper concludes by suggesting that inhibiting the mitochondrial branched-chain amino acid aminotransferase (the first enzyme responsible for the activation of sycamore maple protoxins) could be a possible therapeutic approach for equine atypical myopathy.

Cite This Article

APA
Sander J, Terhardt M, Janzen N, Renaud B, Kruse CJ, François AC, Wouters CP, Boemer F, Votion DM. (2023). Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy. Animals (Basel), 13(15). https://doi.org/10.3390/ani13152410

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 13
Issue: 15

Researcher Affiliations

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
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Kruse, Caroline-Julia
  • Department of Functional Sciences, Physiology and Sport Medicine, Faculty of Veterinary Medicine, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
François, Anne-Christine
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Wouters, Clovis P
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Boemer, François
  • Biochemical Genetics Laboratory, Human Genetics, CHU Sart Tilman, University of Liège, 4000 Liège, Belgium.
Votion, Dominique-Marie
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.

Conflict of Interest Statement

The authors declare no conflict of interest.

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