Background Erythropoietic Protoporphyria (EPP) is an inherited metabolic disorder due to ferrochelatase activity deficiency and it is characterized by the accumulation of protoporphyrin IX (PPIX) in erythrocytes, plasma and tissues. PPIX is a photosensitizer agent that can cause cytotoxic oxidative damage directly or through the generation of Reactive Oxygen Species (ROS). Unsatured membrane lipids, including phospholipids and cholesterol are recognized targets of oxidative modifications. Oxidized lipids originating from poly-unsaturated fatty acids (PUFAs) have gained increasing relevance as modulators of inflammation and have been associated with a large number of biological processes including tissue damage.

Aims In order to investigate on PUFAs involvement in patients with EPP, we applied a lipidomics strategy to characterize blood samples taken from these subjects particularly exposed to oxidative damage.

Methods Fatty acid methyl esters profiles were obtained from whole blood samples from 10 EPP patients and 10 controls by a sequential procedure which involved the simultaneous saponification and methylation of bound fatty acids, butylated hydroxytoluene (BHT) derivatization and gas chromatography-mass spectrometry (GC-MS) analysis. Integrated areas of single peaks were extracted from Total Ion Chromatogram (TIC) and used for the quantitative analysis. Fatty acids identification was obtained by matching with spectral library data and verified by comparison with the authentic standards.

Results Whole blood samples were characterized on the basis of their content of PUFAs including arachidonic acid (AA), linoleic acid (LA), dihomo-gamma-linoleic acid (DGLA), alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Blood samples from EPP patients showed increased ratio of omega-6/omega-3 PUFA by comparison with controls thus indicating higher consumption of omega-3 PUFA to support the synthesis of pro-inflammatory lipid mediators.

Conclusion This work represents a first step towards a deeper characterization of lipid asset in EPP patients since this topic is fundamental for a full comprehension of inflammatory processes underlying the clinical manifestations of EPP.