Micro- and nanoplastics induce hepatic injury through organelle stress and fibrotic signaling: mechanisms and therapeutic opportunities

Micro- and nanoplastics (MNPs) have emerged as widespread environmental contaminants and are increasingly being detected in human tissues, including the liver. As the primary organ responsible for detoxification and metabolic regulation, the liver is particularly vulnerable to the accumulation of these particles following gastrointestinal absorption and systemic distribution. Growing evidence suggests that MNPs are not biologically inert but actively interfere with intracellular homeostasis, leading to progressive hepatic injury. This review summarizes current evidence on the mechanisms by which MNPs contribute to liver dysfunction, with a particular focus on organelle stress and fibrotic signaling. Following cellular uptake, MNPs accumulate within hepatocytes and Kupffer cells, where they disrupt mitochondrial function, induce excessive reactive oxygen species production, trigger endoplasmic reticulum stress, and impair lysosomal degradation and autophagic clearance. These interconnected disturbances form an organelle stress network that promotes persistent cellular dysfunction. The resulting oxidative and proteostatic stress activates inflammatory pathways, including NF-κB and the NLRP3 inflammasome, leading to sustained production of pro-inflammatory cytokines and amplification of hepatic injury. Chronic inflammation and unresolved intracellular stress subsequently drive activation of hepatic stellate cells through profibrotic mediators such as transforming growth factor-β (TGF-β) and Smad signaling, resulting in extracellular matrix deposition and progressive fibrotic remodeling. We propose an integrated framework linking MNP physicochemical properties, hepatic accumulation, organelle dysfunction, inflammatory amplification, and fibrosis development. In addition, emerging therapeutic strategies targeting oxidative stress, inflammasome activation, autophagy dysfunction, and the gut–liver axis are discussed. The current evidence supports the view that MNPs function as persistent intracellular stressors capable of initiating and sustaining pathways associated with chronic liver disease. A better understanding of these mechanisms will be essential for risk assessment and for the development of effective preventive and therapeutic interventions.