Concentration Dependent Influence of Lipopolysaccharides on Separation of Hoof Explants and Supernatant Lactic Acid Concentration in an Ex Vivo/In Vitro Laminitis Model.
Authors: Reisinger Nicole, Schaumberger Simone, Nagl Veronika, Hessenberger Sabine, Schatzmayr Gerd
Journal: PloS one
Summary
# Editorial Summary: Lipopolysaccharide Effects on Hoof Tissue Integrity and Metabolism Endotoxins (lipopolysaccharides or LPS) are increasingly suspected of playing a central role in laminitis pathogenesis, yet their precise mechanisms of action on lamellar tissue remain poorly characterised. Reisinger and colleagues employed an ex vivo model using isolated equine hoof explants and cells, exposing them to five escalating LPS concentrations (0–100 µg/mL) whilst measuring tissue integrity through mechanical separation force and evaluating metabolic function via volatile fatty acid and glucose analysis. The critical findings revealed that whilst LPS showed no direct cytotoxic effects on epidermal or dermal hoof cells, it significantly compromised tissue integrity in a dose-dependent manner—explants treated with 10 and 100 µg/mL required substantially less force to separate—and distinctly suppressed lactic acid production at the higher concentrations. This dissociation between intact cell viability and impaired tissue cohesion suggests LPS may disrupt the extracellular matrix and cell-cell adhesion mechanisms within the lamellae rather than causing acute cellular death, whilst the depression of anaerobic lactate metabolism points to potential mitochondrial dysfunction or shifts in cellular respiration. For practitioners, these findings underscore that endotoxaemia's contribution to laminitis may centre on architectural destabilisation of lamellar attachments and metabolic derangement rather than straightforward cell necrosis, with clear implications for understanding how systemic infections and colitis precipitate clinical laminitis and informing prophylactic strategies during high-risk inflammatory states.
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Practical Takeaways
- •Endotoxemia may compromise lamellar tissue integrity through mechanisms other than direct cell death, supporting aggressive endotoxin management in at-risk horses
- •The dose-dependent effect of LPS on tissue separation suggests that endotoxin load correlates with lamellar failure risk; monitoring and controlling systemic endotoxemia is critical in laminitis prevention
- •Altered lactic acid metabolism in affected tissue may represent a useful biomarker for early lamellar compromise and warrants further investigation for diagnostic or prognostic application
Key Findings
- •LPS concentrations of 10 and 100 µg/mL significantly reduced the force required to separate hoof explants, indicating compromised tissue integrity in a dose-dependent manner
- •LPS treatment did not cause direct cytotoxicity to isolated epidermal or dermal hoof cells
- •Lactic acid concentrations were significantly decreased in explants exposed to 5, 10, or 100 µg/mL LPS, suggesting altered energy metabolism in lamellar tissue
- •LPS impairs hoof tissue integrity without killing individual cells, implicating endotoxins as a contributing factor to laminitis pathogenesis