Effects of xylazine and dexmedetomidine on equine articular chondrocytes in vitro.
Abstract: To assess the effects of xylazine and dexmedetomidine on equine chondrocytes, in vitro. Methods: Prospective, experimental study. Methods: Equine articular chondrocytes from five male horses. Methods: Chondrocytes were isolated from healthy equine articular cartilage of the metacarpo/metatarsophalangeal joints. Cell viability was assessed using the WST-8 assay by exposing chondrocytes to xylazine (0.5, 1, 2, 4, 8, 16.6, 25, 50 mg mL) or dexmedetomidine (0.001, 0.005, 0.01, 0.05, 0.175, 0.25 mg mL) for 15, 30 and 60 minutes. Based on the results of these tests, cells were treated with xylazine (1, 4, 25 mg mL) or dexmedetomidine (0.05, 0.175, 0.25 mg mL) for 15 minutes to further evaluate: cell viability by neutral red uptake; cell membrane integrity by lactate dehydrogenase release and by fluorescence microscopy with Hoechst 33342 and propidium iodide (PI), and apoptosis by flow cytometry using double staining with annexin V-fluorescein isothiocyanate/PI and by cell morphology. Results: Both drugs reduced cell viability in a dose-dependent manner. Specifically, all xylazine concentrations, except 0.5 mg mL and 1 mg mL, significantly reduced cell viability, whereas the effects of dexmedetomidine were evident only at 0.175 mg mL and 0.25 mg mL. The highest concentrations of xylazine (25 mg mL) and dexmedetomidine (0.25 mg mL) caused loss of membrane integrity. Cell morphology and flow cytometry analyses demonstrated signs of late apoptosis in xylazine-treated cells, and signs of late apoptosis and necrosis in dexmedetomidine-treated cells. Conclusions: This study offers new insights into the potential chondrotoxicity induced by dexmedetomidine and xylazine. Therefore, the intra-articular administration of α-agonists should be conducted with care, especially for doses of ≥ 4 mg mL of xylazine and 0.175 mg mL and 0.25 mg mL of dexmedetomidine.
Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
Publication Date: 2017-01-17 PubMed ID: 28259429DOI: 10.1016/j.vaa.2016.04.004Google Scholar: Lookup
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- Journal Article
Summary
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The research article explores the effects of two drugs, xylazine and dexmedetomidine, on horse chondrocytes in laboratory conditions. It discovers that these drugs can reduce cell viability and cause loss of membrane integrity, raising concerns about their potential chondrotoxicity.
Objective and Methods
- The primary aim was to investigate the impact of xylazine and dexmedetomidine on equine chondrocytes in vitro.
- Chondrocytes, the only cells in cartilage, were extracted from the joint cartilage of five male horses.
- The cells were exposed to varying concentrations of each drug for different durations, ranging between 15 and 60 minutes.
- The WST-8 assay was used to evaluate cell viability, a test that indicates how many cells remained alive after the treatment.
Additional Evaluations
- Following initial tests, the cells were also treated with certain concentrations of xylazine or dexmedetomidine for 15 minutes.
- The neutral red uptake test was used to further measure cell viability.
- Cell membrane integrity was assessed using two methods: measuring the release of lactate dehydrogenase enzyme and using fluorescence microscopy with dyes Hoechst 33342 and propidium iodide.
- They also examined apoptosis or cell death using flow cytometry and observing cell morphology.
Results
- Both drugs were found to reduce cell viability in a dose-dependent manner, i.e., the higher the concentration, the larger the decrease in cell survival.
- Xylazine significantly decreased cell viability at almost all tested concentrations, while dexmedetomidine showed similar effects only at the highest concentrations.
- The highest tested concentrations of both drugs resulted in a loss of membrane integrity, a critical aspect of cell survival.
- Microscopy and cytometry analysis indicated late apoptosis in cells subjected to xylazine, whereas dexmedetomidine-treated cells showed signs of both late apoptosis and necrosis (cell death).
Conclusions
- In light of these findings, the researchers suggest careful administration of these drugs, especially at high concentrations. This is due to their potential chondrotoxic impact, which could harm chondrocytes.
- This study contributes valuable insights into the potential risks associated with using these drugs in equine veterinary practice, particularly when administered directly into joints.
Cite This Article
APA
Mancini F, Nannarone S, Buratta S, Ferrara G, Stabile AM, Vuerich M, Santinelli I, Pistilli A, Chiaradia E.
(2017).
Effects of xylazine and dexmedetomidine on equine articular chondrocytes in vitro.
Vet Anaesth Analg, 44(2), 295-308.
https://doi.org/10.1016/j.vaa.2016.04.004 Publication
Researcher Affiliations
- Laboratory of Proteomics and Cellular Biochemistry, Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sport Horse Research Centre, Department of Veterinary Medicine, University of Perugia, Perugia, Italy; Veterinary Teaching Hospital, Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Laboratory of Biochemistry and Molecular Biology, Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy.
- Laboratory of Biochemistry and Molecular Biology, Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy.
- Laboratory of Anatomy, Department of Surgery and Biomedical Sciences, University of Perugia, Perugia, Italy.
- Veterinary Teaching Hospital, Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Veterinary Teaching Hospital, Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Laboratory of Anatomy, Department of Surgery and Biomedical Sciences, University of Perugia, Perugia, Italy.
- Laboratory of Proteomics and Cellular Biochemistry, Department of Veterinary Medicine, University of Perugia, Perugia, Italy; Sport Horse Research Centre, Department of Veterinary Medicine, University of Perugia, Perugia, Italy. Electronic address: elisabetta.chiaradia@unipg.it.
MeSH Terms
- Adrenergic alpha-2 Receptor Agonists / administration & dosage
- Adrenergic alpha-2 Receptor Agonists / pharmacology
- Animals
- Cartilage, Articular / cytology
- Cell Membrane / drug effects
- Cell Survival / drug effects
- Chondrocytes / drug effects
- Dexmedetomidine / pharmacology
- Horses
- In Vitro Techniques / veterinary
- Male
- Prospective Studies
- Tetrazolium Salts / pharmacology
- Xylazine / pharmacology
Citations
This article has been cited 8 times.- Arévalo-Turrubiarte M, Baratta M, Ponti G, Chiaradia E, Martignani E. Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro. Equine Vet J 2022 Nov;54(6):1133-1143.
- Akça B, Ankay Yılbaş A, Üzümcügil F, Büyükakkuş B, Bahador Zırh E, Zeybek D, Sarıcaoğlu F. How does intraarticular dexmedetomidine injection effect articular cartilage and synovium? An animal study. BMC Anesthesiol 2020 Sep 17;20(1):237.
- Kim EN, Lee HS, Jeong GS. Cudratricusxanthone O Inhibits H(2)O(2)-Induced Cell Damage by Activating Nrf2/HO-1 Pathway in Human Chondrocytes. Antioxidants (Basel) 2020 Aug 25;9(9).
- Chiaradia E, Pepe M, Orvietani PL, Renzone G, Magini A, Sforna M, Emiliani C, Di Meo A, Scaloni A. Proteome Alterations in Equine Osteochondrotic Chondrocytes. Int J Mol Sci 2019 Dec 7;20(24).
- Castellini C, Mattioli S, Dal Bosco A, Collodel G, Pistilli A, Stabile AM, Macchioni L, Mancuso F, Luca G, Rende M. In vitro effect of nerve growth factor on the main traits of rabbit sperm. Reprod Biol Endocrinol 2019 Nov 12;17(1):93.
- Zhou L, Zhou J, Sheng B, Li X, Yuan Y. Dexmedetomidine exerts dual effects on human annulus fibrosus chondrocytes depending on the oxidative stress status. Biosci Rep 2019 Aug 30;39(8).
- Di Salvo A, Chiaradia E, Della Rocca G, Giorgi M, Mancini F, Marenzoni ML, Conti MB, Nannarone S. Efficacy, chondrotoxicity and plasma concentrations of tramadol following intra-articular administration in horses undergoing arthroscopy: preliminary findings. Vet Q 2018 Dec;38(1):129-137.
- Guidoni K, Chiaradia E, Pepe M, Di Meo A, Tognoloni A, Seccaroni M, Beccati F. The Combined Use of Triamcinolone and Platelet-Rich Plasma in Equine Metacarpophalangeal Joint Osteoarthritis Treatments: An In Vivo and In Vitro Study. Animals (Basel) 2024 Dec 17;14(24).
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