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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 18, 2013
Effect of triorganotin compounds on membrane permeability
Antonio Ortiz1, José A Teruel, Francisco J Aranda
1Departamento de Bioquímica y Biología Molecular A, Facultad de Veterinaria, Universidad de Murcia, Campus de Espinardo, E-30100, Murcia, Spain.
Biochimica Et Biophysica Acta
|February 14, 2006
Summary
Triorganotin compounds, like tributyltin, disrupt cell membranes, causing leakage of molecules and red blood cell hemolysis. This toxicity is linked to anion exchange across membranes, particularly involving chloride.
Area of Science:
- Environmental Toxicology
- Membrane Biophysics
- Biochemistry
Background:
- Organotin compounds are pervasive environmental toxicants known for their membrane activity and broad biological toxicity.
- Understanding their interaction with biological membranes is crucial for assessing their toxicological impact.
Purpose of the Study:
- To investigate the effects of triorganotin compounds on membrane permeability using model phospholipid membranes and human erythrocytes.
- To elucidate the mechanism by which organotins affect membrane integrity and ion transport.
Main Methods:
- Utilized large unilamellar vesicles (LUVs) with entrapped carboxyfluorescein to assess membrane permeability changes induced by tribultyltin and triphenyltin.
- Examined the influence of lipid composition (phosphatidylcholine, phosphatidylserine, cholesterol) and external anions (gluconate, chloride) on carboxyfluorescein release.
- Investigated the hemolytic effects of tributyltin on human erythrocytes, monitoring potassium leakage and hemoglobin release.
- Assessed hemolysis in different external media (gluconate vs. chloride) to understand anion involvement.
Main Results:
- Tribultyltin and triphenyltin induced carboxyfluorescein release from LUVs, with similar rates across different phospholipid compositions.
- Cholesterol reduced the rate of carboxyfluorescein release, indicating a role in membrane stabilization.
- Carboxyfluorescein release was inhibited by gluconate and restored by chloride, suggesting anion exchange.
- Tributyltin caused dose-dependent hemolysis of human erythrocytes, with potassium leakage occurring concurrently with hemoglobin release.
- Hemolysis was reduced in gluconate-based media, further supporting the role of anion transport.
Conclusions:
- Triorganotin compounds facilitate the transport of organic anions across phospholipid bilayers via exchange diffusion with chloride.
- Anion exchange across the erythrocyte membrane is implicated in the mechanism of organotin-induced hemolysis.
- These findings highlight a specific mechanism for organotin toxicity related to membrane transport processes.
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