Hepatotoxic effects of environmentally relevant concentrations of polystyrene microplastics on senescent Zebrafish (Danio rerio): Patterns of stress response and metabolomic alterations

The hepatotoxicity of microplastics (MPs) has garnered increasing attention, but their effects on elderly organisms remain inadequately characterized, particularly concerning hepatic stress response patterns in environmental conditions. In this study, a 10-day exposure period of elderly zebrafish to polystyrene microplastics (PS-MPs, 1 µm) was conducted, with exposure concentrations set at 5.6 × 10⁻⁷ µg/L, 5.6 × 10⁻⁴ µg/L, and 5.6 × 10⁻¹ µg/L. PS-MPs-induced toxicity varied with concentration: superoxide dismutase (SOD), complement 3 (C3), and complement 4 (C4) initially decreased before rising; 8‑hydroxy-2-deoxyguanosine (8-OhdG), interleukin-6 (IL-6), and interleukin-8 (IL-8) increased at high concentrations. Additionally, catalase (CAT) activity and thiobarbituric acid reactive substances (TBARS) contents rose with concentration. The aged zebrafish liver exhibited differentiation driven by responsiveness; low levels cause homeostatic disruption, and high levels induce genotoxicity and immune activation. LC-MS identified twelve crucial metabolites involved in 18 metabolic pathways, including amino acids (L-tyrosine, l-arginine), lipids (phospholipids, 12(S)-leukotriene B4 and triglycerides), and N-acetylneuraminic acid, related to energy, immunity, and neurological health. Overall, elderly zebrafish exhibited clear dose-dependent thresholds and distinct physiological stress responses under varying concentrations of PS-MPs. These findings reveal how PS-MP exposure can affect physiological health and metabolism, offering critical insights into the ecological risks faced by aging organisms.