Modulating effects of acepromazine on the reactive oxygen species production by stimulated equine neutrophils.
Abstract: To investigate the effect of acepromazine (ACP) on reactive oxygen species (ROS) production by stimulated equine neutrophils. Methods: Ex vivo biochemical experiments. Methods: Isolated neutrophils from healthy untreated horses. Methods: Neutrophils were incubated with ACP at concentrations of 10(-4), 10(-5) or 10(-6) M and then stimulated with phorbol-myristate-acetate (PMA) before measurement of lucigenin-enhanced chemiluminescence (CL). In a second experiment neutrophils were incubated in the presence of α-keto-γ methylthiobutyric acid (KMB) and treated with ACP at concentrations of 10(-4), 10(-5) or 10(-6) M. Subsequent PMA stimulation lead to neutrophilic ROS production and decomposition of KMB to ethylene, which is measured by gas chromatography. Electron paramagnetic resonance-spin trapping (EPR) analysis was performed with PMA-stimulated neutrophils in the presence of ACP (10(-4), 10(-5) or 10(-6) M) directly added to the cell suspension. In the second experiment, the same concentrations of ACP were pre-incubated with neutrophils, then centrifuged to eliminate the excess of ACP and re-suspended in phosphate buffer before stimulation with PMA. In all experiments, the results of ACP-treated and ACP-untreated stimulated neutrophils were compared. Results: Overall, results obtained with lucigenin-enhanced CL and KMB oxidation were in agreement with those seen in electron paramagnetic resonance spectroscopy. Acepromazine induced a dose-dependent inhibitory effect on neutrophilic ROS production. Electron paramagnetic resonance also showed, at high ACP concentration, the appearance of a cation radical derived from ACP. In contrast, electron paramagnetic resonance study performed with pre-incubated neutrophils showed an important dose-dependent inhibitory effect of ACP. Conclusions: The results indicate that ACP can neutralize O.-2 or its by-products during the stimulation of neutrophils. Conclusions: These findings may have a therapeutic relevance when phenothiazines are used in horses suffering from inflammatory diseases in which neutrophil activation and ROS production are implicated.
© 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.
Publication Date: 2011-02-10 PubMed ID: 21303439DOI: 10.1111/j.1467-2995.2010.00583.xGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research investigates the effect of acepromazine on the production of reactive oxygen species by stimulated horse neutrophils, revealing a dose-dependent inhibitory effect that could have therapeutic relevance in managing inflammatory diseases in horses.
Research Methodology
- The researchers employed ex vivo biochemical experiments, using neutrophils isolated from untreated, healthy horses for their study.
- The isolated neutrophils were subjected to various concentrations of acepromazine (ACP), following which they were stimulated with phorbol-myristate-acetate (PMA).
- A lucigenin-enhanced chemiluminescence (CL) method was used to measure the effect. In a parallel experiment, neutrophils were incubated with α-keto-γ methylthiobutyric acid (KMB), then treated with ACP and subsequently stimulated with PMA.
- Neutrophilic ROS production led to the decomposition of KMB to ethylene, which was measured via gas chromatography.
- Electron paramagnetic resonance-spin trapping (EPR) analysis was performed with PMA-stimulated neutrophils, both directly in presence of ACP, and with neutrophils pre-incubated with ACP, centrifuged to eliminate excess ACP, and then re-suspended in phosphate buffer before stimulating with PMA.
Results
- The outcomes from the lucigenin-enhanced CL and KMB oxidation experiments were in agreement with the results seen in the electron paramagnetic resonance spectroscopy.
- Acepromazine was observed to induce a dose-dependent inhibitory effect on neutrophilic reactive oxygen species production.
- The EPR analysis showed the emergence of a cation radical derived from ACP at high concentrations. However, when the study was performed with pre-incubated neutrophils, a significant dose-dependent inhibitory effect of ACP was observed.
Conclusions
- From the results, it was concluded that acepromazine has the ability to neutralize O.-2 or its by-products during the neutrophils’ stimulation.
- The researchers suggest that these findings can have therapeutic implications, particularly when phenothiazines are being used in the treatment of horses suffering from inflammatory diseases. This is because the activation of neutrophils and the production of reactive oxygen species are implicated in such conditions.
Cite This Article
APA
Sandersen C, Mouithys-Mickalad A, de la Rebière G, Deby G, Serteyn D, Franck T.
(2011).
Modulating effects of acepromazine on the reactive oxygen species production by stimulated equine neutrophils.
Vet Anaesth Analg, 38(2), 83-93.
https://doi.org/10.1111/j.1467-2995.2010.00583.x Publication
Researcher Affiliations
- Equine Clinic, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium. charlotte.sandersen@ulg.ac.be
MeSH Terms
- Acepromazine / pharmacology
- Animals
- Dose-Response Relationship, Drug
- Electron Spin Resonance Spectroscopy / veterinary
- Ethylenes / biosynthesis
- Horses
- Hypnotics and Sedatives / pharmacology
- Luminescent Measurements
- Methionine / analogs & derivatives
- Methionine / pharmacology
- Neutrophils / drug effects
- Neutrophils / metabolism
- Oxidation-Reduction / drug effects
- Reactive Oxygen Species / antagonists & inhibitors
- Tetradecanoylphorbol Acetate / pharmacology
Citations
This article has been cited 2 times.- Hernández-Avalos I, Flores-Gasca E, Mota-Rojas D, Casas-Alvarado A, Miranda-Cortés AE, Domínguez-Oliva A. Neurobiology of anesthetic-surgical stress and induced behavioral changes in dogs and cats: A review. Vet World 2021 Feb;14(2):393-404.
- Pequito M, Amory H, de Moffarts B, Busoni V, Serteyn D, Sandersen C. Evaluation of acepromazine-induced hemodynamic alterations and reversal with norepinephrine infusion in standing horses. Can Vet J 2013 Feb;54(2):150-6.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
