Protective Effects of 3′-Epilutein and 3′-Oxolutein against Glutamate-Induced Neuronal Damage

Dietary lutein can be naturally metabolized to 3′-epilutein and 3′-oxolutein in the human body. The epimerization of lutein can happen in acidic pH, and through cooking, 3′-epilutein can be the product of the direct oxidation of lutein in the retina, which is also present in human serum. The 3′-oxolutein is the main oxidation product of lutein. Thus, the allylic oxidation of dietary lutein can result in the formation of 3′-oxolutein, which may undergo reduction either to revert to dietary lutein or epimerize to form 3′-epilutein. We focused on the effects of 3′-epilutein and 3′-oxolutein itself and on glutamate-induced neurotoxicity on SH-SY5Y human neuroblastoma cells to identify the possible alterations in oxidative stress, inflammation, antioxidant capacity, and iron metabolism that affect neurological function. ROS measurements were performed in the differently treated cells. The inflammatory state of cells was followed by TNFα, IL-6, and IL-8 cytokine ELISA measurements. The antioxidant status of the cells was determined by the total antioxidant capacity kit assay. The alterations of genes related to ferroptosis and lipid peroxidation were followed by gene expression measurements; then, thiol measurements were performed. Lutein metabolites 3′-epilutein and 3′-oxolutein differently modulated the effect of glutamate on ROS, inflammation, ferroptosis-related iron metabolism, and lipid peroxidation in SH-SY5Y cells. Our results revealed the antioxidant and anti-inflammatory features of 3′-epilutein and 3′-oxolutein as possible protective agents against glutamate-induced oxidative stress in SH-SY5Y cells, with greater efficacy in the case of 3′-epilutein.