A lipidomic approach towards identifying the effects of fragrance hydroperoxides on keratinocytes

BackgroundLimonene and linalool are used in cosmetic products for their floral scents, but their oxidation products are strong contact allergens whose mechanisms of action are still not fully understood.ObjectivesThe effects of limonene hydroperoxide (Lim-2-OOH) and linalool hydroperoxides (Lin-6/7-OOH) on the lipid profile of a human keratinocyte cell line (HaCaT) were evaluated. 2,4-Dinitrofluorobenzene (DNFB) was also included.MethodsLim-2-OOH and Lin-6/7-OOH were synthesised according to previous methods. HaCaT cells were treated with allergens (10 mu M) for 24 h and the cellular lipid extracts were analysed by C18 liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data analysis was performed using Lipostar software. Statistical analysis was carried out using Metaboanalyst and R software.ResultsAll three sensitisers used caused significant changes in the lipidome of HaCaT cells in a similar trend. There was an upregulation in several plasmanyl/plasmenyl phospholipids (O-/P-phosphatidylcholines [PC] and O-/P-phosphatidylethanolamines [PE]), sphingolipids (HexCer) and triacylglycerol lipid species, and a decrease in some polyunsaturated fatty acids-containing phospholipid (PE and PC) species suggesting oxidative stress and inflammation.ConclusionsThis study is the first to evaluate the plasticity of the HaCaT cell lipidome in response to allylic hydroperoxide allergens Lim-2-OOH and Lin-6/7-OOH, together with the experimental contact allergen DNFB. These allergens are able to upregulate and downregulate certain lipid classes to a varying degree.This research investigates the response of a human keratinocyte cell line lipidome to two hydroperoxide allergens: limonene hydroperoxide (Lim-2-OOH) and linalool hydroperoxide (Lin-6/7-OOH). Several plasmanyl/plasmenyl phospholipids, sphingolipids and triacylglycerol lipid species were upregulated. In contrast, there was a decrease in several polyunsaturated fatty acids-containing phospholipid species. image