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The haemolytic effect of verapamil on erythrocytes exposed to varying osmolarity.

Abstract: The haemolytic effect of verapamil on red blood cells (RBCs) exposed to varying osmolarity was investigated. The experimental approach used a modified red cell haemolysis assay with concentrations of verapamil ranging from 50-1500 microM compared to drug free controls. The time-course of haemolytic effects was also investigated. We also briefly determined the haemolytic effects of verapamil in Ca2+-free conditions (with added EGTA). In conditions representing decreasing osmolarity (dilution from 140-0 mM NaCl) there was a significant increase in erythrocyte haemolysis that was also dependent on verapamil concentration (ANOVA, p<0.05). The red cells also showed a significantly increased rate of haemolysis over 5 h with increasing verapamil concentration (ANOVA, p<0.05). The degree of RBC hypotonic haemolysis was significantly increased in a Ca2+-free medium (+EGTA) compared to normal saline and this effect was exacerbated by additions of verapamil (ANOVA, p<0.05). Overall the data suggested that verapamil can cause haemolysis of RBCs in a predictable time- and concentration-dependent manner, and that verapamil increases the fragility of the erythrocytes further during hypotonic osmotic stress and Ca2+-free conditions. The mechanism of verapamil-dependent haemolysis could be directly related to the observed biphasic concentration-effect and could consequently involve several ion transport pathways.
Publication Date: 2007-02-20 PubMed ID: 17398066DOI: 10.1016/j.tiv.2007.02.002Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates the destructive effect of verapamil, a medication used to treat high blood pressure and heart diseases, on red blood cells (erythrocytes) when subjected to varying salt concentrations (osmolarity). The study finds that verapamil induces the breakage (hemolysis) of the cells more intensely under specific conditions, such as low osmolarity and absence of calcium in the environment.

Introduction

  • The study primarily focuses on analyzing how verapamil affects red blood cells under different salt concentration levels, termed as osmolarity, using assay tests.
  • By changing the osmolarity of the red blood cells environment, they mimic the conditions these cells might encounter in the body due to varying salt concentrations.

Methodology

  • Concentrations of verapamil ranged from 50-1500 microM were used in the experiment.
  • The researchers also measured the hemolytic effects over time to understand if there is any time-dependency for this effect.
  • The effects of an absence of calcium ions, often present in the body, were also investigated by creating a calcium-free environment using EGTA, a chelating agent.

Results

  • It was observed that the hemolytic effect increased significantly with decreasing osmolarity, meaning as the environment became more dilute, more red blood cells were destroyed. This effect was further heightened with higher concentrations of verapamil.
  • Over the course of 5 hours, the rate of red blood cell destruction significantly increased with increasing verapamil concentration.
  • In a calcium-free environment, the hemolytic effect of verapamil was exacerbated.

Conclusion

  • The research concludes that the drug verapamil has a predictable time- and concentration-dependent effect on the hemolysis of red blood cells.
  • It was further concluded that the fragility of these cells increased when they were exposed to a low osmotic stress condition and an environment without calcium.
  • The manner in which verapamil promotes hemolysis might be directly tied to the biphasic concentration-effect observed during the study, which could involve multiple ion transport pathways.

Cite This Article

APA
Watts TJ, Handy RD. (2007). The haemolytic effect of verapamil on erythrocytes exposed to varying osmolarity. Toxicol In Vitro, 21(5), 835-839. https://doi.org/10.1016/j.tiv.2007.02.002

Publication

ISSN: 0887-2333
NlmUniqueID: 8712158
Country: England
Language: English
Volume: 21
Issue: 5
Pages: 835-839

Researcher Affiliations

Watts, T J
  • School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, United Kingdom. timwatts1984@yahoo.co.uk
Handy, R D

    MeSH Terms

    • Animals
    • Calcium / metabolism
    • Calcium / physiology
    • Calcium Channel Blockers / toxicity
    • Chelating Agents / pharmacology
    • Dose-Response Relationship, Drug
    • Egtazic Acid / pharmacology
    • Erythrocytes / drug effects
    • Hemolysis / drug effects
    • Horses
    • Hypotonic Solutions
    • In Vitro Techniques
    • Kinetics
    • Osmolar Concentration
    • Verapamil / toxicity

    Citations

    This article has been cited 1 times.
    1. Xia Q, Zhang Y, Li Z, Hou X, Feng N. Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application.. Acta Pharm Sin B 2019 Jul;9(4):675-689.
      doi: 10.1016/j.apsb.2019.01.011pubmed: 31384529google scholar: lookup