Polycyclic aromatic hydrocarbons can trigger hepatocyte release of extracellular vesicles by various mechanisms of action depending on their affinity for the aryl hydrocarbon receptor.

Extracellular vesicles (EVs) are membrane enclosed nanostructures released by cells into the extracellular environment. As major actors of physiological intercellular communication, they have been shown to be pathogenic mediators of several liver diseases. EVs also appear to be potential actors of drug-induced liver injury, but nothing is known concerning environmental pollutants. We aimed to study the impact of polycyclic aromatic hydrocarbons (PAHs), major contaminants, on hepatocyte-derived EV production, with a special focus on hepatocyte death. Three PAHs were selected, based on their presence in food and their affinity for the aryl hydrocarbon receptor (AhR): benzo(a)pyrene (BP), dibenzo(a,h)anthracene (DBA), and pyrene (PYR). Treatment of primary rat and WIF-B9 hepatocytes by all three PAHs increased the release of EVs, mainly comprised of exosomes, in parallel with modifying exosome protein marker expression and inducing apoptosis. Moreover, PAH treatment of rodents for three mo...