Microplastics cause tissue damage by inducing apoptosis, oxidative damage, and inflammatory responses in zebrafish: a meta-analysis

The toxicity of microplastics (MPs) to aquatic organisms has caused widespread public concern in recent years. Zebrafish, a common model organism, have been extensively employed to assess the impact of MPs on biological health. However, existing research findings exhibit heterogeneity and lack quantitative integration and systematic clarification. To address this issue, the study employed meta-analysis to establish, for the first time, a cross-study quantitative framework for MP toxicity pathways. MP exposure resulted in reduced activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase by 4.8%, 6.5%, and 17.2%, respectively, and induced compensatory upregulation of the detoxification enzyme glutathione S-transferase (17.6%). Reactive oxygen species (ROS) levels increased by 52.7%, subsequently activating the tumor suppressor p53 signaling (expression up-regulated by 124.1%) and inducing apoptosis, with cysteine aspartic acid protease 9 and cysteine aspartic acid protease 3 activities enhanced by 54.2% and 50.0%, respectively. Simultaneously, it confirmed the concurrent activation of cellular oxidative damage (34% increase in lipid peroxidation) and inflammatory response (32.3% upregulation of tumor necrosis factor-α expression). This study performed a quantitative integration analysis based on statistical association. It reconciled heterogeneity within the literature. Furthermore, it established and validated a quantitative adverse outcome pathway for the first time. This pathway was demonstrated to be conserved across different experimental systems. It provides the first data-driven quantitative mechanistic framework for understanding the toxicity of MPs and identifies key targets for subsequent experimental validation.