Lutein reduces cisplatin-induced intestinal inflammation by inhibiting ROS-mediated MAPK/NF-κB pathways

Cisplatin is a commonly used chemotherapy drug that can effectively treat a variety of cancers, but it often causes severe side effects, including nephrotoxicity, ototoxicity, and gastrointestinal toxicity, which significantly affects patients' quality of life. Lutein is a natural carotenoid known for its potent antioxidant properties. Recent literature supports the beneficial effects of lutein supplements in conditions such as retinal degeneration, cardiovascular disease, and liver damage, emphasizing its broad anti-inflammatory capabilities. However, the mechanism by which cisplatin causes intestinal inflammation and the protective effect of lutein against this remain unknown. Here, we investigated the potential protective effect of lutein against cisplatin-induced intestinal epithelial injury. Our results proved that cisplatin significantly decreased cell viability, enhanced ROS generation, and activated inflammatory signaling pathways involving p38, ERK, and NF-κB in IEC-6 cells. Pretreatment with lutein markedly suppressed ROS production, reduced p38 and ERK phosphorylation, prevented NF-κB activation, and consequently attenuated inflammatory cytokine expression. These findings establish lutein as a promising dietary strategy to reduce cisplatin-induced intestinal inflammation, supporting its therapeutic potential for improving chemotherapy tolerance.