MSCs-derived exosomes attenuate cadmium-induced hepatotoxicity by suppressing mitochondria-dependent ferroptosis

Cadmium (Cd) is a ubiquitous environmental toxicant that poses a persistent threat to the liver. Although Cd exposure has been closely linked to various liver diseases, effective and safe therapeutic interventions remain lacking. In this study, we investigated the protective effects of mesenchymal stem cell-derived exosomes (MSCs-Exos) against Cd-induced hepatotoxicity. Mechanistically, we​ identified​ that Cd triggers mitochondria-dependent ferroptosis, characterized by mitochondrial fragmentation, loss of membrane potential, and depletion of key antioxidant defenses. MSCs-Exos effectively reverse these alterations by restoring mitochondrial integrity, reducing reactive oxygen species and iron accumulation, and rebalancing the expression of ferroptosis regulators and mitochondrial integrity-associated factors. In vivo, systemically administered MSCs-Exos home to the injured liver, alleviate Cd-induced elevations in liver enzymes, and attenuate hepatic inflammation, necrosis, and ultrastructural mitochondrial damage. Together, these results indicate that MSCs-Exos protect against Cd-induced liver injury by suppressing mitochondria-dependent ferroptosis, highlighting their therapeutic potential for Cd-associated hepatotoxicity.