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Toxicol In Vitro ; 27(1): 339-48, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22940465

RESUMO

We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals: lyral and lilial. Whereas both chemicals exerted a significant effect on primary keratinocyte(s), HaCat cells, no effect was obtained with any of HepG2, Hek293, Caco2, NIH3T3, and MCF7 cells. Lyral and lilial: (a) decreased the viability of HaCat cells with a 50% cell death at 100 and 60 nM respectively; (b) decreased significantly in a dose dependant manner the intracellular ATP level following 12-h of treatment; (c) inhibited complexes I and II of electron transport chain in liver sub-mitochondrial particles; and (d) increased reactive oxygen species generation that was reversed by N-acetyl cysteine and trolox and the natural antioxidant lipoic acid, without influencing the level of free and/or oxidized glutathione. Lipoic acid protected HaCat cells against the decrease in viability induced by either compound. Dehydrogenation of lyral and lilial produce α,ß-unsaturated aldehydes, that reacts with lipoic acid requiring proteins resulting in their inhibition. We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain, increase ROS production, derange mitochondrial membrane potential, and decrease cellular ATP level, leading thus to cell death.


Assuntos
Aldeídos/toxicidade , Cicloexenos/toxicidade , Perfumes , Acetilcisteína/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromanos/farmacologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Glutationa/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Camundongos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Células NIH 3T3 , Espécies Reativas de Oxigênio/metabolismo , Ácido Tióctico/farmacologia
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