The function of the Nrf2/GPX4 ferroptosis pathway in liver damage caused by lead sulfide nanoparticles

Lead sulfide nanoparticles (PbS NPs) are important nanomaterials for photovoltaic cells and photocatalysts. PbS NPs are widely recognized to induce liver damage; however, the toxicological mechanism remains ambiguous. The Nrf2-mediated antioxidant response element signaling system is a crucial antioxidant mechanism that protects cells from oxidative damage in rats. This study utilised 40 rats to establish a model for PbS NPs exposure, administering PbS NPs at 4 incremental dose levels (0, 25, 50, and 100 mg/kg). The findings indicated that exposure to PbS NPs could elevate lead levels, augment reactive oxygen species, diminish Adenosine Triphosphate and glutathione concentrations, and reduce catalase activity in the liver. Moreover, reactive oxygen species reduced the mRNA and protein expression levels of Nrf2, GPX4, HO-1, and SLC7A11. Furthermore, significant pathomorphological alterations were discovered in liver tissue, including ballooning degeneration of hepatocytes. Ultrastructural analysis revealed that the nucleolus volume of hepatocytes decreased, the nuclear membrane boundary blurred, and the mitochondria appeared vacuolated. Therefore, PbS NPs could enter the blood circulation through gavage, accumulate in the liver, and cause liver damage by inducing iron death in liver cells. Overall, our findings indicated that the ferroptosis signaling pathway is involved in liver injury induced by PbS NPs, providing novel mechanistic evidence for understanding the hepatotoxicity of PbS NPs.