Identification of neurotoxicity markers induced by realgar exposure in the mouse cerebral cortex using lipidomics

Abstract

Realgar is a traditional Chinese medicine containing arsenic and has neurotoxicity. This study used realgar exposure mice model, neurobehavioral tests, analytical chemistry, molecular biology and nontargeted lipidomics to explore the mechanism of realgar damages the nervous system. The arsenic contained in realgar passed through the BBB and accumulated in the brain. Neurons, synapses and myelin showed abnormal changes in the cerebral cortex. The number of autophagosomes were incresed as well as levels of MDA, Lp-PLA2, and cPLA2 but the CAT level was significant reduced. Finally, the cognition and memory of mice were decreased. Nontargeted lipidomics detected 34 lipid subclasses including 1603 lipid molecules. The levels of the LPC and LPE were significantly increased. Under the condition of variable importance for the projection (VIP)>1 and P < 0.05, only 28 lipid molecules satisfied the criteria. The lipid molecular markers SM (d36:2), PE (18:2/22:6) and PE (36:3) which were filtered by receiver operating characteristic (ROC) curve (AUC>0.8 or AUC<0.2) were used to identify the neurotoxicity induced by realgar. Therefore, realgar induces neurotoxicity through exacerbating oxidative damage and lipid dysfunction. Providing research basis for the clinical diagnosis and treatment of realgar-induced neurotoxicity.

Keywords: Arsenic; Lipidomics; Neurotoxicity; Realgar.