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Mitochondrial effects of triarylmethane dyes
A J Kowaltowski1, J Turin, G L Indig
1Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brazil.
Journal of Bioenergetics and Biomembranes
|February 22, 2000
Summary
Triarylmethane dyes impact mitochondrial respiration and membrane potential. Some dyes act as protonophores, while others induce permeability transition, affecting cell viability.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Triarylmethane dyes are investigated for antioncotic photodynamic therapy.
- Mitochondria are key targets for cancer treatment due to their role in cellular energy and apoptosis.
Purpose of the Study:
- To investigate the mitochondrial effects of six triarylmethane dyes at submicromolar concentrations.
- To differentiate the mechanisms by which these dyes affect mitochondrial function, specifically respiration and membrane potential.
Main Methods:
- Studied the effects of dyes on glutamate, succinate, and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) supported mitochondrial respiration.
- Assessed mitochondrial membrane potential dissipation and swelling in isolated mitochondria.
- Investigated the role of calcium (EGTA, Mg2+) and mitochondrial permeability transition pore (cyclosporin A) in dye-induced effects.
Main Results:
- All six dyes inhibited glutamate or succinate-supported respiration, with photodynamic enhancement.
- Victoria blue dyes (R, B, BO) acted as protonophores, uncoupling mitochondria by increasing proton permeability.
- Ethyl violet, crystal violet, and malachite green induced mitochondrial permeability transition, leading to respiratory inhibition via cytochrome c release, driven by NAD(P)H oxidation.
Conclusions:
- Triarylmethane dyes exhibit distinct mechanisms of mitochondrial toxicity.
- Victoria blue dyes function as protonophores, while other dyes trigger the mitochondrial permeability transition.
- These findings are crucial for understanding the therapeutic potential and side effects of these dyes in antioncotic photodynamic therapy.