title: Fragrance chemicals lyral and lilial decrease viability of HaCat cells' by increasing free radical production and lowering intracellular ATP level: protection by antioxidants.
abstract: 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,β-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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. justa@aub.edu.lb
authors.forename: Julnar
authors.initials: J
authors.lastname: Usta
authors.forename: Yassmine
authors.initials: Y
authors.lastname: Hachem
authors.forename: Omar
authors.initials: O
authors.lastname: El-Rifai
authors.forename: Yolla
authors.initials: Y
authors.lastname: Bou-Moughlabey
authors.forename: Karim
authors.initials: K
authors.lastname: Echtay
authors.forename: David
authors.initials: D
authors.lastname: Griffiths
authors.forename: Hania
authors.initials: H
authors.lastname: Nakkash-Chmaisse
authors.forename: Rajaa Fakhoury
authors.initials: RF
authors.lastname: Makki
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D053138:Cyclohexenes / Q000633:toxicity*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D041681:NIH 3T3 Cells; D010476:Perfume; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D002839:Chromans; D053138:Cyclohexenes; D045222:Electron Transport Chain Complex Proteins; D010476:Perfume; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; C092244:hydroxyisohexyl 3-cyclohexene carboxaldehyde; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C038018:lilial; D000111:Acetylcysteine