Effect of sugar metabolite methylglyoxal on equine lamellar explants: An ex vivo model of laminitis.
Abstract: Laminitis is one of the most devastating diseases in equine medicine, and although several etiopathogenetic mechanisms have been proposed, few clear answers have been identified to date. Several lines of evidence point towards its underlying pathology as being metabolism-related. In the carbonyl stress pathway, sugars are converted to methylglyoxal (MG)-a highly reactive α-oxoaldehyde, mainly derived during glycolysis in eukaryotic cells from the triose phosphates: D-glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. One common hypothesis is that MG could be synthesized during the digestive process in horses, and excessive levels absorbed into peripheral blood could be delivered to the foot and lead to alterations in the hoof lamellar structure. In the present study, employing an ex vivo experimental design, different concentrations of MG were applied to hoof explants (HE), which were then incubated and maintained in a specific medium for 24 and 48 h. Macroscopic and histological analyses and a separation force test were performed at 24 and 48 h post-MG application. Gene expression levels of matrix metalloproteinase (MMP)-2 and -14 and tissue inhibitor of metalloproteinase (TIMP)-2 were also measured at each time point for all experimental conditions. High concentrations of MG induced macroscopic and histological changes mimicking laminitis. The separation force test revealed that hoof tissue samples incubated for 24 h in a high concentration of MG, or with lower doses but for a longer period (48 h), demonstrated significant weaknesses, and samples were easily separated. All results support that high levels of MG could induce irreversible damage in HEs, mimicking laminitis in an ex vivo model.
Publication Date: 2021-07-27 PubMed ID: 34314429PubMed Central: PMC8315528DOI: 10.1371/journal.pone.0253840Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the effect of sugar metabolite methylglyoxal (MG) on equine lamellar explants, suggesting a potential link between high MG levels and the development of laminitis, a severe horse disease, using an ex-vivo model.
Background
- The study looks into laminitis, one of the most damaging diseases in equine medicine. Despite extensive research, clear answers and solutions have been hard to find.
- The researchers paid attention to evidence that implied that this condition could be metabolism-related. They focused on a biological process known as carbonyl stress pathway, where sugars are converted to methylglyoxal, a highly reactive α-oxoaldehyde.
- They explored the hypothesis that MG could be produced during a horse’s digestion process and, if absorbed into the blood in excessive levels, it may cause alterations in the hoof lamellar structure, potentially leading to laminitis.
Methodology
- Using an ex vivo experimental design, the researchers applied different concentrations of MG to hoof explants (HE) and then incubated them in a specific medium for 24 and 48 hours.
- The effects were studied using macroscopy, histology, a separation force test and gene expression levels of matrix metalloproteinase (MMP)-2 and -14, and tissue inhibitor of metalloproteinase (TIMP)-2 at the 24h and 48h intervals.
Findings
- High MG concentrations induced macroscopic and histological changes that resembled laminitis.
- The force testing showed that hoof tissue samples incubated in a high concentration of MG for 24 hours, or in lower concentrations for 48 hours, were significantly weaker and could be easily separated, suggesting tissue damage.
- Overall, the results supported the hypothesis that high concentrations of MG could impose irreversible damage on hoof explants, manifesting similar conditions to laminitis in an ex vivo setting.
Cite This Article
APA
Vercelli C, Tursi M, Miretti S, Giusto G, Gandini M, Re G, Valle E.
(2021).
Effect of sugar metabolite methylglyoxal on equine lamellar explants: An ex vivo model of laminitis.
PLoS One, 16(7), e0253840.
https://doi.org/10.1371/journal.pone.0253840 Publication
Researcher Affiliations
- Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.
- Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.
- Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.
- Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.
- Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.
- Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.
- Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.
MeSH Terms
- Animals
- Gene Expression / drug effects
- Hoof and Claw / cytology
- Hoof and Claw / metabolism
- Hoof and Claw / pathology
- Horses
- Male
- Matrix Metalloproteinase 14 / genetics
- Matrix Metalloproteinase 14 / metabolism
- Matrix Metalloproteinase 2 / genetics
- Matrix Metalloproteinase 2 / metabolism
- Models, Biological
- Pyruvaldehyde / analysis
- Pyruvaldehyde / metabolism
- Pyruvaldehyde / pharmacology
- Sugars / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / genetics
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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Citations
This article has been cited 1 times.- Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K. Equine Metabolic Syndrome: A Complex Disease Influenced by Multifactorial Genetic Factors.. Genes (Basel) 2023 Jul 27;14(8).
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