Mechanisms underlying mitochondrial dysfunction and intestinal damage induced by ingestion of microplastics in Leuciscus waleckii: The role of the NF-κB/Nrf2 signaling pathway

Abstract

This study investigates the impact of polystyrene microplastics (PS-MPs) on the growth, immunity, oxidative stress, mitochondrial function, and intestinal health of Leuciscus waleckii (3.00±0.02 g) juveniles over 8 weeks. Our findings indicate that exposure to PS-MPs negatively affected the growth of Leuciscus waleckii, resulting in digestive disturbances. Furthermore, PS-MPs triggered immune dysfunction and oxidative stress through the activation of the NF-κB pathway and suppression of the Nrf2 signaling cascade. PS-MPs damaged intestinal tissue and compromised the intestinal barrier. Additionally, mitochondrial homeostasis was disrupted, activating endogenous mitochondrial apoptotic pathways, ultimately leading to cell apoptosis. High-throughput 16S rRNA sequencing disclosed that PS-MPs provoked shifts in the intestinal microbiota. Mantel analysis indicates significant correlations between growth parameters and the activities of enzymes related to antioxidant defense, immunity, apoptosis, and mitochondria, as well as with the gut microbiota. In summary, our study reveals that PS-MPs induce intestinal inflammation and oxidative stress in Leuciscus waleckii by activating the NF-κB pathway and the intrinsic mitochondrial apoptotic pathway while repressing the Nrf2 signaling, ultimately leading to cellular apoptosis, mitochondrial dysfunction, intestinal microbiota imbalance, and growth inhibition.