Toxic cascade from oxidative stress to metabolic imbalance in Manila clams exposed to polyethylene terephthalate microplastics.

Polyethylene terephthalate (PET) is one of the most abundant plastic pollutants in marine environments. However, compared with other polymers, research on PET microplastics (MPs)-particularly their impact on benthic organisms in sediment environments-remains relatively scarce. In this study, we exposed Manila clams (Ruditapes philippinarum) to PET MPs in fragments and fibers of five sizes at concentrations of 0.8, 8, and 80 mg/kg dry weight (dw) of sediment for 21 days using a water-sediment exposure system. Mortality in Manila clams exposed to PET MPs remained unchanged, and each MP group accumulated in the digestive glands and gills. Chronic exposure to PET MPs increased reactive oxygen species production and SOD, IL-1β, and CASP8 levels in the gill and digestive gland tissues of clams. Integrated biomarker response analysis showed stronger correlations for fragments than for fibers, and for larger than smaller sizes, in both gill and digestive gland tissues. Furthermore, omics analysis confirmed a strong response in inflammation-related factors to fragment MPs, suggesting that PET MPs induce oxidative stress, inflammation, and cellular responses that lead to digestive and secretory dysfunction, which may cause morphological and metabolic changes in clams and ultimately adversely affect their health and survival. This study contributes to our understanding of the toxic mechanisms of PET MPs, focusing on their size and shape, and ultimately raises awareness of their harmful effects in the environment.