Hepatic and metabolic outcomes induced by sub-chronic exposure to polystyrene microplastics in mice.

Abstract

Microplastics (MPs) have attracted significant attention due to their global distribution in living environments. Although some studies have reported MP-induced hepatotoxicity in mouse models, a systematic approach to MP-mediated liver toxicity was still lacking. Therefore, we used a mouse model to study the sub-chronic effects of MP exposure on the liver. Female C57BL/6 mice, aged 6weeks, received an oral administration of 0.3mg of Nile Red-labeled polystyrene (PS) microplastics, with particle sizes of 0.5µm (submicron) and 5µm (micron), via gavage, while control mice received vehicle only. Each mouse was exposed to MPs twice a week for 12weeks. After sacrifice, the levels of MP accumulation, oxidative stress, inflammation, and pathological changes were measured in the mouse liver, and blood samples were collected for serum biochemistry analysis. Our results demonstrated that 0.5µm PS-MPs were accumulated in mouse livers post-MP exposure, but not in the 5µm MP exposure group. Simultaneously, increased levels of glucose, triglyceride, alanine transaminase (ALT), aspartate transaminase (AST), superoxide dismutase, 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), interleukin-6, and lipid droplets were found in the 0.5µm MP exposure group, while the fewer responses, including elevated liver weight index, glucose, high-density lipoprotein, AST, and decreased HNE-MA were observed in 5µm MP exposure group. These results indicate that sub-chronic exposure to submicron MPs causes MP deposition in mouse livers, which further induces oxidative stress, increases inflammatory cytokines and perturbs glucose and lipid homeostasis, which might trigger more severe metabolic dysfunction or non-alcoholic steatohepatitis-like hepatotoxicity.