Mitochondrial effects of triarylmethane dyes.
The mitochondrial effects of submicromolar concentrations of six triarylmethane dyes, with potential applications in antioncotic photodynamic therapy, were studied. All dyes promoted an inhibition of glutamate or succinate-supported respiration in uncoupled mitochondria, in a manner stimulated photodynamically. No inhibition of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) supported respiration was observed, indicating that these dyes do not affect mitochondrial complex IV. When mitochondria were energized with TMPD in the absence of an uncoupler, treatment with victoria blue R, B, or BO, promoted a dissipation of mitochondrial membrane potential and increase of respiratory rates, compatible with mitochondrial uncoupling. This effect was observed even in the dark, and was not prevented by EGTA, Mg2+ or cyclosporin A, suggesting that it is promoted by a direct effect of the dye on inner mitochondrial membrane permeability to protons. Indeed, victoria blue R, B, and BO promoted swelling of valinomycin-treated mitochondria incubated in a hyposmotic K+-acetate-based medium, confirming that these dyes act as classic protonophores such as FCCP. On the other hand, ethyl violet, crystal violet, and malachite green promoted a dissipation of mitochondrial membrane potential, accompanied by mitochondrial swelling, which was prevented by EGTA, Mg2+, and cyclosporin A, demonstrating that these drugs induce mitochondrial permeability transition. This mitochondrial permeabilization was followed by respiratory inhibition, attributable to cytochrome c release, and was caused by the oxidation of NAD(P)H promoted by these drugs.
Kowaltowski
A J
AJ
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brazil.
Turin
J
J
Indig
G L
GL
Vercesi
A E
AE
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology*; D005840:Gentian Violet / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008086:Lissamine Green Dyes / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009995:Osmosis / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D017319:Photosensitizing Agents / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D012394:Rosaniline Dyes / Q000494:pharmacology*; D013772:Tetramethylphenylenediamine / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology
D004396:Coloring Agents; D008086:Lissamine Green Dyes; D017319:Photosensitizing Agents; D000644:Quaternary Ammonium Compounds; D012394:Rosaniline Dyes; C005095:malachite green; D014634:Valinomycin; C034752:Basic Blue K; C084160:Victoria blue BO; D018698:Glutamic Acid; C034887:ethyl violet; D005840:Gentian Violet; D013772:Tetramethylphenylenediamine; D001205:Ascorbic Acid; C009662:Victoria blue B