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farriery
veterinary
biomechanics
anatomy
nutrition
physiotherapy
2020
Expert Opinion

Amikacin induces rapid dose-dependent apoptotic cell death in equine chondrocytes and synovial cells in vitro.

Authors: Pezzanite Lynn, Chow Lyndah, Soontararak Sirikul, Phillips Jennifer, Goodrich Laurie, Dow Steven

Journal: Equine veterinary journal

Summary

# Editorial Summary: Amikacin Toxicity in Equine Joint Cells Intra-articular aminoglycoside injections are routine in equine practice, deployed both for septic arthritis management and as adjunctive therapy during osteoarthritis treatment, yet their safety profile against the joint's resident cell populations remained uncharacterised. Pezzanite and colleagues conducted an in vitro study exposing equine chondrocytes and synovial cells to amikacin across a range of concentrations to establish dose-dependent toxicity thresholds and mechanisms of cell death. The results demonstrated rapid, concentration-dependent apoptosis in both cell types, with significant cell death occurring at clinically relevant doses—findings that directly contradict the implicit safety assumptions underlying current intra-articular dosing practices. Given that chondrocytes and synovial cells are essential to joint homeostasis and repair, these findings warrant urgent reassessment of aminoglycoside protocols in equine orthopaedics, particularly regarding dosing, duration of exposure, and suitability for use in non-septic joint conditions where alternative antimicrobials or anti-inflammatory agents might offer efficacy without sacrificing resident joint cell viability.

Read the full abstract on PubMed

Practical Takeaways

  • Intra-articular aminoglycoside use requires careful dose consideration as toxicity to joint resident cells has been demonstrated and safe dosing protocols are not yet established
  • When treating septic arthritis or co-injecting with osteoarthritis medications, veterinarians should weigh the antimicrobial benefits against demonstrated chondrocyte and synovial cell toxicity
  • Further in vivo studies are needed to establish safe intra-articular aminoglycoside dosing protocols for equine joint injections

Key Findings

  • Amikacin induces rapid dose-dependent apoptotic cell death in equine chondrocytes and synovial cells in vitro
  • Safe and effective intra-articular doses of aminoglycosides have not been previously defined in equine medicine
  • Aminoglycosides demonstrate toxicity to equine mesenchymal stem cells and resident joint cells

Conditions Studied

septic arthritisosteoarthritisintra-articular aminoglycoside toxicity

Related References

Evaluation of Intra-Articular Amikacin Administration in an Equine Non-inflammatory Joint Model to Identify Effective Bactericidal Concentrations While Minimizing Cytotoxicity.

Pezzanite Lynn, Chow Lyndah, Hendrickson Dean, Gustafson Daniel L, Russell Moore A, Stoneback Jason, Griffenhagen Gregg M, Piquini Gabriella, Phillips Jennifer, Lunghofer Paul, Dow Steven, Goodrich Laurie R(2021)Frontiers in veterinary science

Intra-articular administration of antibiotics in horses: Justifications, risks, reconsideration of use and outcomes.

Pezzanite Lynn M, Hendrickson Dean A, Dow Steven, Stoneback Jason, Chow Lyndah, Krause Danielle, Goodrich Laurie(2022)Equine veterinary journal

Use of in vitro assays to identify antibiotics that are cytotoxic to normal equine chondrocytes and synovial cells.

Pezzanite Lynn, Chow Lyndah, Piquini Gabriella, Griffenhagen Gregg, Ramirez Dominique, Dow Steven, Goodrich Laurie(2021)Equine veterinary journal

The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells.

Bohannon L K, Owens S D, Walker N J, Carrade D D, Galuppo L D, Borjesson D L(2013)Equine veterinary journal

Inflammatory response to the administration of mesenchymal stem cells in an equine experimental model: effect of autologous, and single and repeat doses of pooled allogeneic cells in healthy joints.

Ardanaz N, Vázquez F J, Romero A, Remacha A R, Barrachina L, Sanz A, Ranera B, Vitoria A, Albareda J, Prades M, Zaragoza P, Martín-Burriel I, Rodellar C(2016)BMC veterinary research