Polystyrene micro- and nanoplastics induce gastric toxicity through ROS mediated oxidative stress and P62/Keap1/Nrf2 pathway

• Published in: The Science of the total environment Vol. 912; p. 169228
• Main Authors: Sun, Rongli, Liu, Manman, Xiong, Fei, Xu, Kai, Huang, Jiawei, Liu, Jinyan, Wang, Daqin, Pu, Yuepu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.02.2024
• Subjects: Adverse outcome pathway; Animals; Gastric toxicity; Humans; Kelch-Like ECH-Associated Protein 1; Mice; Microplastics; NF-E2-Related Factor 2; Nuclear factor-E2-related factor 2; Oxidative Stress; Plastics; Polystyrenes - toxicity; Reactive Oxygen Species; ROS; Stomach; Microplastics; Gastric toxicity; Nuclear factor-E2-related factor 2; ROS; Adverse outcome pathway
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2023.169228

Microplastics (MPs) exist widely in the environment and can enter the human body indirectly through the food chain or directly through inhalation or ingestion. The primary organ that MPs contaminated food or water enters the human body through the digestive tract is the stomach. However, at present, the effects of MPs on the stomach and the related mechanism remain unclear. In this study, our results indicated that 50 nm and 250 nm polystyrene MPs (PS-MPs) at environmental related dose significantly decreased stomach organ coefficient, inhibited gastric juice secretion and mucus secretion, disrupted gastric barrier function and suppressed antioxidant ability in mice. In vitro experiments showed that PS-MPs inhibited cell viability, increased ROS generation, and induced apoptosis through mitochondria-dependent pathway. Simultaneously, PS-MPs also decreased mitochondrial membrane potential, ATP level, disrupted mitochondrial kinetic homeostasis, and activated P62 / Nrf2 / Keap1 pathway. Furthermore, blocking ROS (NAC) partially alleviated ROS and apoptosis caused by PS-MPs. Based on above findings, the potential adverse outcome pathway (AOP) of PS-MPs-caused gastric toxicity was proposed which provides a new insight into the risk assessment of MP related gastric damage. Our study unveils the gastric injury induced by PS MPs is dependent on ROS - mediated P62 / Nrf2 / Keap1 signaling pathway, and provides scientific basis for further exploration the mechanism of gastric toxicity of PS MPs. [Display omitted] •MPs disrupt gastric secretion, and damage gastric barrier function in mice.•MPs inhibit cell growth, cause excessive ROS, apoptosis and mitochondria dysfunction.•The P62 / Nrf2 / Keap1 pathway is involved in MP induced gastric toxicity.•50 nm MPs caused severe gastric damage than 250 nm MPs.•The AOP framework of MPs related gastric toxicity is proposed for the first time.