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Fig. 6 | Journal of Nanobiotechnology

Fig. 6

From: Nanomaterials and hepatic disease: toxicokinetics, disease types, intrinsic mechanisms, liver susceptibility, and influencing factors

Fig. 6

Schematic of NM-induced iron and copper toxicity. NMs, such as Si-, NiO-, SiO2- and Cu-NPs, induce iron overload by stimulating hepcidin secretion and activating ERK/MAPK, BMP/SMAD, IL-6, STAT3 signaling. Hepcidin overexpression leads to ferroportin reduction, resulting in iron efflux obstruction. Additionally, IONP exposure leads to liver toxicity by inducing ROS generation via triggering the Fenton reaction. Additionally, IONP exposure leads to increased secretion of ferritin. High concentrations of copper NMs induce CYP450 depression, which aggravates the toxicity of NMs by ROS-mediated activation of NF-κB, MAPK, and STAT3 signaling, as well as overexpression of PXR, CAR and AHR. Cu2+ released from copper NPs is reduced to Cu+, which catalyzes the formation of hydroxyl radicals. Copper overload also results in the depletion of ceruloplasmin, leading to decreased iron efflux and iron overaccumulation. Finally, iron and copper overload-induced excess ROS generation further induces ER stress, inflammation, and mitochondrial stress, resulting in an increased risk of liver diseases

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