Identification of hypoglycin A binding adsorbents as potential preventive measures in co-grazers of atypical myopathy affected horses.
Abstract: Intestinal absorption of hypoglycin A (HGA) and its metabolism are considered major prerequisites for atypical myopathy (AM). The increasing incidence and the high mortality rate of AM urgently necessitate new therapeutic and/or preventative approaches. Objective: To identify a substance for oral administration capable of binding HGA in the intestinal lumen and effectively reducing the intestinal absorption of the toxin. Methods: Experimental in vitro study. Methods: Substances commonly used in equine practice (activated charcoal composition, di-tri-octahedral smectite, mineral oil and activated charcoal) were tested for their binding capacity for HGA using an in vitro incubation method. The substance most effective in binding HGA was subsequently tested for its potential to reduce intestinal HGA absorption. Jejunal tissues of 6 horses were incubated in Ussing chambers to determine mucosal uptake, tissue accumulation, and serosal release of HGA in the presence and absence of the target substance. Potential intestinal metabolism in methylenecyclopropyl acetic acid (MCPA)-conjugates was investigated by analysing their concentrations in samples from the Ussing chambers. Results: Activated charcoal composition and activated charcoal were identified as potent HGA binding substances with dose and pH dependent binding capacity. There was no evidence of intestinal HGA metabolism. Conclusions: Binding capacity of adsorbents was tested in vitro using aqueous solutions, and in vivo factors such as transit time and composition of intestinal content, may affect adsorption capacity after oral administration. Conclusions: For the first time, this study identifies substances capable of reducing HGA intestinal absorption. This might have major implications as a preventive measure in cograzers of AM affected horses but also in horses at an early stage of intoxication.
© 2017 EVJ Ltd.
Publication Date: 2017-09-04 PubMed ID: 28715146DOI: 10.1111/evj.12723Google Scholar: Lookup
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- Journal Article
Summary
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The research article is focused on identifying substances that can bind a toxin known as hypoglycin A (HGA) found in the intestines of horses, as a potential preventative measure against atypical myopathy (AM), a fatal condition in grazers.
Objective
- The main objective of this research was to find a substance that can be orally administered to horses and bind HGA in their intestinal tracts. This binding would preferentially prevent the absorption of HGA, a necessary step leading to the onset of AM.
Methods
- The scientists first carried out an in vitro experiment, testing common substances used in equine practice to see their binding capacity with HGA. The substances used in these tests were activated charcoal composition, di-tri-octahedral smectite, mineral oil and activated charcoal.
- An in vitro incubation technique was used in these tests.
- The substance that was most effective in binding HGA was further tested to measure its potential in reducing intestinal absorption of HGA.
- The further test involved incubating intestinal tissues from 6 horses in Ussing chambers to see how much HGA would be taken up by the tissue, how much would accumulate in the tissue, and how much would be released back out into the serosal (lining of the intestinal wall).
- The researchers also examined any potential for intestinal metabolism into methylenecyclopropyl acetic acid (MCPA) conjugates by the analysis of their concentrations from the Ussing chamber samples.
Results
- The researchers identified activated charcoal composition and activated charcoal as substances that could effectively bind HGA, with the binding capacity being dependent on dose and pH.
- Interestingly, they found no evidence of intestinal metabolism of HGA.
Conclusions
- The in vitro test results provided evidence of the binding capacity of adsorbents. However, it was suggested that in vivo factors, such as the transit time of the substance through the intestines and the composition of intestinal content, might affect the binding capacity after oral administration.
- The study made a significant contribution to the aim of reducing HGA intestinal absorption. This could have important practical implications as a preventative measure in horses that graze together with those affected by AM, or in horses displaying early signs of intoxication.
Cite This Article
APA
Krägeloh T, Cavalleri JMV, Ziegler J, Sander J, Terhardt M, Breves G, Cehak A.
(2017).
Identification of hypoglycin A binding adsorbents as potential preventive measures in co-grazers of atypical myopathy affected horses.
Equine Vet J, 50(2), 220-227.
https://doi.org/10.1111/evj.12723 Publication
Researcher Affiliations
- Department of Physiology, University of Veterinary Medicine Hannover Foundation, Halle, Germany.
- Clinic for Horses, University of Veterinary Medicine Hannover Foundation, Halle, Germany.
- Leibniz Institute of Plant Biochemistry, Halle, Germany.
- Screening-Labor Hannover, Hannover, Germany.
- Screening-Labor Hannover, Hannover, Germany.
- Department of Physiology, University of Veterinary Medicine Hannover Foundation, Halle, Germany.
- Department of Physiology, University of Veterinary Medicine Hannover Foundation, Halle, Germany.
MeSH Terms
- Acer / chemistry
- Adsorption
- Animals
- Antidotes / chemistry
- Antidotes / pharmacology
- Charcoal / administration & dosage
- Charcoal / chemistry
- Charcoal / pharmacology
- Drug Combinations
- Horse Diseases / chemically induced
- Horse Diseases / prevention & control
- Horses
- Hypoglycins / chemistry
- Hypoglycins / toxicity
- Kaolin
- Plant Bark / chemistry
- Plant Poisoning / veterinary
- Quercus / chemistry
- Rhabdomyolysis / chemically induced
- Rhabdomyolysis / veterinary
- Seeds / chemistry
- Silicates / administration & dosage
- Silicates / chemistry
- Silicates / pharmacology
- Silicon Dioxide / administration & dosage
- Silicon Dioxide / chemistry
- Silicon Dioxide / pharmacology
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