FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Veterinary immunology and immunopathology2003; 95(1-2); 11-19; doi: 10.1016/s0165-2427(03)00097-7

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.
Get Full Text
Publication Date: 2003-09-13 PubMed ID: 12969632DOI: 10.1016/s0165-2427(03)00097-7Google 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.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

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

Veterinary immunology and immunopathology
ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 95
Issue: 1-2
Pages: 11-19

Researcher Affiliations

Massoco, C
  • 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.
Palermo-Neto, J

    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

    This article has been cited 16 times.
    1. Wu T, Ma X, Zuo P, Chen S, Tang X, Zhang X, Hou E. Association between benzodiazepines use and lung cancer in U.S. adults: Results from the National Health and Nutrition Examination Survey. Medicine (Baltimore) 2025 Oct 24;104(43):e45357.
      doi: 10.1097/MD.0000000000045357pubmed: 41137248google scholar: lookup
    2. Song D, Tang X, Du J, Tao K, Li Y. Diazepam inhibits LPS-induced pyroptosis and inflammation and alleviates pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis. PLoS One 2024;19(6):e0305409.
      doi: 10.1371/journal.pone.0305409pubmed: 38875245google scholar: lookup
    3. Oh TK, Park HY, Song IA. Insomnia disorder and cancer mortality in South Korea: a secondary analysis of musculoskeletal disease cohort. Sleep Breath 2024 Jun;28(3):1311-1318.
      doi: 10.1007/s11325-024-03009-0pubmed: 38418767google scholar: lookup
    4. Huang KH, Tai CJ, Kuan YH, Chang YC, Tsai TH, Lee CY. Pneumonia Risk Associated with the Use of Individual Benzodiazepines and Benzodiazepine Related Drugs among the Elderly with Parkinson's Disease. Int J Environ Res Public Health 2021 Sep 6;18(17).
      doi: 10.3390/ijerph18179410pubmed: 34501996google scholar: lookup
    5. Foo NP, Liu YF, Wu PC, Hsing CH, Huang BM, So EC. Midazolam's Effects on Delayed-Rectifier K(+) Current and Intermediate-Conductance Ca(2+)-Activated K(+) Channel in Jurkat T-lymphocytes. Int J Mol Sci 2021 Jul 4;22(13).
      doi: 10.3390/ijms22137198pubmed: 34281255google scholar: lookup
    6. Pohlin F, Hooijberg EH, Buss P, Huber N, Viljoen FP, Blackhurst D, Meyer LCR. A Comparison of Hematological, Immunological, and Stress Responses to Capture and Transport in Wild White Rhinoceros Bulls (Ceratotherium simum simum) Supplemented With Azaperone or Midazolam. Front Vet Sci 2020;7:569576.
      doi: 10.3389/fvets.2020.569576pubmed: 33195552google scholar: lookup
    7. Peng TR, Yang LJ, Wu TW, Chao YC. Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies. Medicina (Kaunas) 2020 Oct 1;56(10).
      doi: 10.3390/medicina56100513pubmed: 33019585google scholar: lookup
    8. Atalan G, Atalan G, Erol H, Erol M, Atasever A, Doğan Z, Güneş V, Yönez MK, Keleş I. Comparison of Systemic Effects of Midazolam, Ketamine, and Isoflurane Anaesthesia in Rabbits. J Vet Res 2019 Jun;63(2):275-283.
      doi: 10.2478/jvetres-2019-0035pubmed: 31276068google scholar: lookup
    9. Fang HF, Lee TY, Hui KC, Yim HCH, Chi MJ, Chung MH. Association between Sedative-hypnotics and Subsequent Cancer in Patients with and without Insomnia: A 14-year Follow-up Study in Taiwan. J Cancer 2019;10(10):2288-2298.
      doi: 10.7150/jca.30680pubmed: 31258732google scholar: lookup
    10. Fuller BM, Mohr NM, Roberts BW, Carpenter CR, Kollef MH, Avidan MS. Protocol for a multicentre, prospective cohort study of practice patterns and clinical outcomes associated with emergency department sedation for mechanically ventilated patients: the ED-SED Study. BMJ Open 2018 Oct 21;8(10):e023423.
      doi: 10.1136/bmjopen-2018-023423pubmed: 30344178google scholar: lookup
    11. Wang MT, Wang YH, Chang HA, Tsai CL, Yang YS, Lin CW, Kuo CC, Hsu YJ. Benzodiazepine and Z-drug use and risk of pneumonia in patients with chronic kidney disease: A population-based nested case-control study. PLoS One 2017;12(7):e0179472.
      doi: 10.1371/journal.pone.0179472pubmed: 28692645google scholar: lookup
    12. Ferraz-de-Paula V, Ribeiro A, Souza-Queiroz J, Pinheiro ML, Vecina JF, Souza DP, Quinteiro-Filho WM, Moreau RL, Queiroz ML, Palermo-Neto J. 3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice. J Neuroimmune Pharmacol 2014 Dec;9(5):690-702.
      doi: 10.1007/s11481-014-9562-0pubmed: 25113903google scholar: lookup
    13. Elmesallamy GE, Abass MA, Ahmed Refat NA, Atta AH. Differential effects of alprazolam and clonazepam on the immune system and blood vessels of non-stressed and stressed adult male albino rats. Interdiscip Toxicol 2011 Sep;4(3):132-43.
      doi: 10.2478/v10102-011-0021-ypubmed: 22058654google scholar: lookup
    14. Joya FL, Kripke DF, Loving RT, Dawson A, Kline LE. Meta-analyses of hypnotics and infections: eszopiclone, ramelteon, zaleplon, and zolpidem. J Clin Sleep Med 2009 Aug 15;5(4):377-83.
      pubmed: 19968019
    15. Qiao H, Sanders RD, Ma D, Wu X, Maze M. Sedation improves early outcome in severely septic Sprague Dawley rats. Crit Care 2009;13(4):R136.
      doi: 10.1186/cc8012pubmed: 19691839google scholar: lookup
    16. Koo H, Ryu SH, Ahn HJ, Jung WK, Park YK, Kwon NH, Kim SH, Kim JM, Yoo BW, Choi SI, Davis WC, Park YH. Immunostimulatory effects of the anionic alkali mineral complex Barodon on equine lymphocytes. Clin Vaccine Immunol 2006 Nov;13(11):1255-66.
      doi: 10.1128/CVI.00150-06pubmed: 16943344google scholar: lookup
    Subscribe to our newsletter
    Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.