Moore Aaron I, Moreira Ana S P, Conde Tiago, Melo Tânia, Domingues Pedro, O'Boyle Niamh M, Domingues M Rosário
School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, the University of Dublin, Dublin, Ireland.
CESAM-Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
Contact Dermatitis. 2025 Jul;93(1):16-30. doi: 10.1111/cod.14804. Epub 2025 May 1.
Terpene hydroperoxides are oxidation products of fragrance terpenes commonly found in cosmetic and household products. They are moderate to strong contact allergens associated with allergic contact dermatitis (ACD). Through the cleavage of their oxygen-oxygen bond, they have the potential to induce lipid peroxidation (LPO). However, the role of oxidised lipids in the context of ACD is largely unexplored.
Herein, the capacity of terpene hydroperoxides derived from linalool (Lin-6/7-OOH), geraniol (Ger-6/7-OOH), and limonene (Lim-2-OOH) to induce LPO was evaluated using liposomes in a biomimetic metal-catalysed oxidation system. LPO products were identified and quantified by liquid chromatography-mass spectrometry (LC-MS) and Tandem MS (MS/MS). The C11-BODIPY ratio-fluorescence probe was also used to assess the capacity of terpene hydroperoxides to cause LPO in vitro using a human epidermal keratinocyte cell line (HaCaT).
LC-MS/MS analysis identified 14 LPO products (long-chain and short-chain) formed under metal-catalysed oxidation mediated by terpene hydroperoxides. All hydroperoxides tested at 50 mM caused significant LPO, with Lim-2-OOH exhibiting exceptionally high oxidising potential. The C11-BODIPY ratio-fluorescence assay also revealed higher oxidation associated with Lim-2-OOH.
This work shows the ability of terpene hydroperoxide allergens to cause LPO, raising the possibility that LPO products may act as effectors in the pathogenesis of ACD.
氢过氧化萜类化合物是常见于化妆品和家用产品中的香料萜烯的氧化产物。它们是与过敏性接触性皮炎（ACD）相关的中度至强接触性过敏原。通过其氧-氧键的断裂，它们有可能诱导脂质过氧化（LPO）。然而，氧化脂质在ACD背景下的作用在很大程度上尚未得到探索。
在此，使用脂质体在仿生金属催化氧化系统中评估了源自芳樟醇（Lin-6/7-OOH）、香叶醇（Ger-6/7-OOH）和柠檬烯（Lim-2-OOH）的氢过氧化萜类化合物诱导LPO的能力。通过液相色谱-质谱（LC-MS）和串联质谱（MS/MS）对LPO产物进行鉴定和定量。还使用C11-硼二吡咯比率荧光探针，利用人表皮角质形成细胞系（HaCaT）评估氢过氧化萜类化合物在体外引起LPO的能力。
LC-MS/MS分析鉴定出在氢过氧化萜类化合物介导的金属催化氧化下形成的14种LPO产物（长链和短链）。所有在50 mM测试的氢过氧化物均引起显著的LPO，其中Lim-2-OOH表现出极高的氧化潜力。C11-硼二吡咯比率荧光测定也显示与Lim-2-OOH相关的氧化程度更高。
这项工作表明氢过氧化萜类过敏原具有引起LPO的能力，这增加了LPO产物可能在ACD发病机制中作为效应物的可能性。
