Effects of midazolam on equine innate immune response: a flow cytometric study.
Abstract: Benzodiazepines (BDZ) are among the most frequently used class of psychotropic drugs employed in veterinary medicine in Brazil and worldwide due to their anxiolytic, muscle relaxant and anticonvulsant effects [J. Clin. Pharmacol. 33 (1993) 124]. Peripheral benzodiazepine receptor (PBR) sites were described in peripheral organs, endocrine steroidogenic tissues and immune organs and cells. Midazolam is a mixed-type agonist of PBRs. The present study is focused on the effects of midazolam on equine peripheral blood neutrophils, peritoneal macrophages and cortisol levels in plasma. Adult horses were treated with a single dose of midazolam (0.06 or 0.1 mg/kg) or with 0.9% NaCl. Immune cells were collected 24 h after treatment for flow cytometry analysis of Staphylococcus aureus-induced phagocytosis and oxidative burst. Plasma cortisol concentration was measured 30, 90, 180 and 360 min after midazolam treatment. Midazolam induced a dose-dependent reduction on: (1) peripheral blood neutrophil and peritoneal macrophage oxidative burst; (2) the capacity of both peripheral blood neutrophils and peritoneal macrophages to phagocyte S. aureus. Increments on plasma cortisol concentration were not found after 0.06 and 0.1 mg/kg of midazolam. The effects on oxidative burst of neutrophils and macrophages from horses treated with midazolam were interpreted as a consequence of an impairment of S. aureus-induced phagocytosis. The present data suggest that midazolam, most probably acting on PBRs present on equine macrophage and neutrophil membranes, might have changed some mechanisms related to both phagocytosis and oxidative burst. These results support the use of flow cytometry to identify functional properties and dysfunction of equine immune cells. They also confirm the notion that changes in the functional capacity of the immune system may represent an important hazard of exposure to drugs or chemicals.
Publication Date: 2003-09-13 PubMed ID: 12969632DOI: 10.1016/s0165-2427(03)00097-7Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper focuses on how Midazolam, a commonly used veterinary medication, impacts the immune response in horses, specifically its effects on blood neutrophils, peritoneal macrophages, and cortisol levels. The results show a dose-dependent decrease in certain immune responses and suggest changes in immune system functionality due to drug exposure.
Midazolam and its Impact on Immune Response
- The researchers wanted to understand the effects of midazolam, a drug used in veterinary medicine because of its anxiety-reducing, muscle-relaxing, and anti-convulsive properties. Midazolam acts as a mixed-type agonist on peripheral benzodiazepine receptors (PBRs), which are present in various parts of the body including immune cells.
- The study specifically investigated the effects of midazolam on equine peripheral blood neutrophils, peritoneal macrophages, and cortisol levels. These elements play key roles in the immune response.
The Experimental Process
- Horses were given a single dose of midazolam or a saline solution as a control. Twenty-four hours later, immune cells were collected for analysis, and the cortisol concentration in the plasma was measured at various intervals following the midazolam treatment.
- The effect of midazolam on Staphylococcus aureus-induced phagocytosis and oxidative burst in the immune cells were then tested using flow cytometry.
Observations and Interpretations
- Midazolam was observed to cause a dose-dependent reduction in oxidative burst in both peripheral blood neutrophils and peritoneal macrophages. Additionally, it also diminished the cells’ capacity to phagocytose S. aureus.
- No changes in plasma cortisol concentration were observed after administering midazolam, in contrast to the effects on immune cells.
- The researchers interpreted the reduced capacity for oxidative burst and phagocytosis as an impairment caused by midazolam. They hypothesized that the drug, acting on PBRs present on equine macrophage and neutrophil membranes, might have altered some mechanisms related to these immune responses.
Implication of the Study
- The findings suggest that exposure to certain drugs like midazolam can potentially affect the functional capacity of the immune system. This reinforces the need for careful assessment of the potential risks of drug exposure, particularly in susceptible populations like animals.
- The use of flow cytometry in the study also demonstrates its utility in identifying the functional properties and potential dysfunction of immune cells. This could be a valuable tool for future research in veterinary medicine and immunology.
Cite This Article
APA
Massoco C, Palermo-Neto J.
(2003).
Effects of midazolam on equine innate immune response: a flow cytometric study.
Vet Immunol Immunopathol, 95(1-2), 11-19.
https://doi.org/10.1016/s0165-2427(03)00097-7 Publication
Researcher Affiliations
- Applied Pharmacology and Toxicology Laboratory, Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, School of Veterinary Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.
MeSH Terms
- Anesthetics, Intravenous / blood
- Anesthetics, Intravenous / immunology
- Anesthetics, Intravenous / pharmacology
- Animals
- Female
- Flow Cytometry / veterinary
- Fluoresceins / metabolism
- Horses / immunology
- Hydrocortisone / blood
- Hydrocortisone / immunology
- Immunity, Innate / drug effects
- Macrophages, Peritoneal / drug effects
- Macrophages, Peritoneal / immunology
- Male
- Midazolam / blood
- Midazolam / immunology
- Midazolam / pharmacology
- Neutrophils / drug effects
- Neutrophils / immunology
- Phagocytosis / drug effects
- Phagocytosis / immunology
- Propidium / metabolism
- Respiratory Burst / drug effects
- Respiratory Burst / immunology
Citations
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