Liang Boxuan, Huang Xiyun, Li Zhiming, Huang Yuji, Deng Yanhong, Chen Xiaoqing, Zhong Yizhou, Yang Xiaohong, Feng Yu, Bai Ruobing, Fan Bingchi, Xian Hongyi, Li Hao, Tang Shiyue, Huang Zhenlie
National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China; Department of Cardiovascular Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Environ Int. 2025 Mar;197:109367. doi: 10.1016/j.envint.2025.109367. Epub 2025 Mar 6.
The widespread environmental presence of nanoplastics (NPs) raises significant concerns about their health impacts, particularly on the gastrointestinal system, as NPs are primarily ingested. While previous studies have linked NP-induced intestinal toxicity to oxidative stress and reactive oxygen species (ROS) accumulation, the specific mechanisms of cell death remain unclear. Here, we showed that environmentally relevant concentrations of polystyrene nanoplastics (PS-NPs) induced ferroptosis, a form of lipid peroxidation-driven cell death, in intestinal epithelial cells. Using intestinal epithelial-specific Nrf2-deficient mice (Nrf2-Vil) and human intestinal epithelial Caco-2 cells, we demonstrated that Nrf2, a key oxidative stress regulator, play a protective role against PS-NP-induced ferroptosis. PS-NP exposure disrupted ether phospholipid metabolism, leading to the accumulation of polyunsaturated fatty acid-ether phospholipids and heightened lipid peroxidation in the intestines of Nrf2-Vil mice. This accumulation increased the susceptibility of intestinal epithelial cells to ferroptosis. Additionally, a high-fat diet further exacerbated this effect, suggesting that individuals with reduced NRF2 activity and poor dietary habits may be especially vulnerable to PS-NP-induced intestinal damage. Our findings offered new insights into the molecular mechanisms of NP-induced intestinal toxicity and underscored the health risks posed by environmental PS-NP exposure, particularly in populations with compromised antioxidant defenses.
纳米塑料（NPs）在环境中广泛存在，这引发了人们对其健康影响的重大担忧，尤其是对胃肠道系统的影响，因为纳米塑料主要是通过摄入进入人体的。虽然先前的研究已将纳米塑料诱导的肠道毒性与氧化应激和活性氧（ROS）积累联系起来，但细胞死亡的具体机制仍不清楚。在此，我们表明，环境相关浓度的聚苯乙烯纳米塑料（PS-NPs）在肠道上皮细胞中诱导了铁死亡，这是一种由脂质过氧化驱动的细胞死亡形式。利用肠道上皮特异性Nrf2缺陷小鼠（Nrf2-Vil）和人肠道上皮Caco-2细胞，我们证明了关键氧化应激调节因子Nrf2对PS-NP诱导的铁死亡起到保护作用。PS-NP暴露扰乱了醚磷脂代谢，导致多不饱和脂肪酸醚磷脂在Nrf2-Vil小鼠肠道中积累，并加剧脂质过氧化。这种积累增加了肠道上皮细胞对铁死亡的易感性。此外，高脂饮食进一步加剧了这种影响，这表明NRF2活性降低且饮食习惯不良的个体可能特别容易受到PS-NP诱导的肠道损伤。我们的研究结果为纳米塑料诱导肠道毒性的分子机制提供了新的见解，并强调了环境中PS-NP暴露带来的健康风险，尤其是在抗氧化防御能力受损的人群中。
