Abstract: Objective To explore lipid biomarkers and potential intervention targets for skin toxicity caused by iodixanol. Methods Forty-eight patients using iodixanol in our hospital were selected and divided into a no rash group and a rash group, with 24 cases in each group. Lipid mass spectrometry was adopted to detect the serum of patients with skin toxicity of iodixanol, differentially expressed lipid molecules were analyzed using Metaboanalyst 6.0 software, and the receiver operating characteristic curve (ROC) was drawn. Subsequently, lipid metabolism related genes and transcriptome sequencing results related to skin toxicity were downloaded from the molecular signatures database (MSigDB) and the National Center for Biotechnology Information (NCBI) in the United States, and the intersections of the above two datasets were examined to identify potential lipid metabolism targets associated with iodixanol induced rash. Results Compared with patients without rash, the lipid profile results showed that a total of 198 lipids were identified. After the screening of differential lipid components, 67 lipid components with significant differences were finally identified, including diacylglycerol (DG), triacylglycerol (TG), bis-monoacylglycerol-phosphate (BMP), cholesterol esters (CE), and phosphatidylethanolamine (PE). Compared with patients without rash, the levels of DG, TG, BMP, CE, and PE in the serum of patients with rash were significantly increased while the levels of alkyl-phosphatidylcholine [PC (O)], plasmenyl-phosphatidylcholine [PC (P)], and ether-linked phosphatidylethanolamine [PE (O)] were significantly decreased. Among the top 20 differentially expressed lipid molecules, lipid molecules of TG were dominating, accounting for 55% (11/20). ROC analysis showed that the screened differential lipid components had good predictability (AUC>0.800). Further analysis revealed that among the top 20 differentially expressed genes, proteolipid protein2 (PLP2) showed the most significant increase. Conclusion Levels of lipid TG may be a potential biomarker mediating the occurrence of skin rash caused by iodixanol, and the mechanism may be related to the abnormal upregulation of lipid metabolism gene PLP2 expression.

Key words: Ioxanol, Rash, Lipidomics, Diacylglycerol, Triacylglycerol, Bis-Monoacylglycerol-Phosphate, Cholesterol Esters, Phosphatidylethanolamine, Proteolipid Protein 2