Polystyrene Microplastics Trigger Liver Damage Through Impaired Mitochondrial Biogenesis and Mitochondrial Dynamics

Polystyrene microplastics (PS-MPs) are emerging environmental contaminants with increasing evidence of systemic toxicity; however, the mechanisms underlying their hepatic effects remain incompletely understood. The present study investigated the hepatotoxic effects of PS-MPs, focusing on hepatic bioaccumulation, mitochondrial homeostasis, inflammation, apoptosis, and liver functional impairment. Experimental animals were exposed to increasing concentrations of PS-MPs, after which liver tissues were subjected to GC-MS, biochemical, histopathological, and molecular analyses. GC-MS confirmed hepatic accumulation of PS-MPs predominantly in the higher exposure groups (20 and 40 μg), which were subsequently selected for mechanistic investigations. PS-MP exposure induced marked hepatic dysfunction, evidenced by elevated bilirubin, ALT, AST, and GGT levels together with significant reductions in total protein, albumin, and globulin concentrations. Histopathological examination revealed progressive hepatocellular degeneration, inflammatory infiltration, cytoplasmic vacuolation, and necrotic alterations. In parallel, inflammatory and apoptotic signaling were significantly activated, as demonstrated by increased NF-κB and caspase-3 levels. Mechanistically, PS-MPs were associated with transcriptional dysregulation of genes involved in mitochondrial homeostasis, including suppression of mitochondrial biogenesis markers (PGC-1α and TFAM), downregulation of mitochondrial fusion regulators (MFN2 and OPA1), increased DRP1 expression, and reduced PINK1 expression, suggesting altered mitophagy-related signaling. Principal Component Analysis further demonstrated clear separation between control and exposed groups, strongly associating PS-MP exposure with hepatic injury, transcriptional dysregulation of mitochondrial homeostasis-related genes, inflammation, and apoptosis. Collectively, these findings demonstrate that PS-MPs induce significant hepatotoxicity, accompanied by coordinated transcriptional dysregulation of mitochondrial homeostasis-related genes and activation of inflammatory and apoptotic pathways. These findings highlight the liver as a major target of microplastic toxicity and emphasize the need for further studies incorporating protein-level validation, functional mitochondrial assessments, and long-term exposure models to better understand the implications for human health.