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. Highlights Fragrant chemicals lyral/lilial decreased viability of HaCat cells. ► lyral/lilial-decreased ATP level and increased: ROS level and LDH release in HaCat cells. ► Lyral/lilial inhibited liver sub-mitochondrial particles complexes I and II activities of respiratory chain. ► Antioxidants restored control ROS level; lipoic acid protected the viability of lilial and lyral treated Hacat cells. ► Lyral and lilila are mitochondriotoxin with direct and indirect effect on HaCat cells.