Combined toxicity of Fe₃O₄ nanoparticles and cadmium chloride in mice

Nanomaterials have been widely used in diverse areas. Heavy metals are ubiquitous environmental pollutants. In spite of the real risk of humans' co-exposure to nanoparticles and heavy metals, their combined toxicity has received little attention. We have reported that silica nanoparticles and CdCl₂ have a positive synergistic toxicity in mice. Here, we demonstrate that Fe₃O₄ nanoparticles (nano-Fe₃O₄) and CdCl₂ have a negative synergistic toxicity in mice. Nano-Fe₃O₄ showed low toxicity in mice. In contrast, CdCl₂ caused significant oxidative damage mainly in the liver as indicated by severe liver dysfunction and histopathological abnormalities. Co-exposure to nano-Fe₃O₄ and CdCl₂ significantly attenuated CdCl₂-induced damage in the liver through reduction of oxidative stress. Nano-Fe₃O₄ and CdCl₂ had negative cooperative effects on the biodistributions of Fe and Cd in mice due to mutually competitive inhibition of Fe and Cd uptake. The reduction of Cd accumulation in tissues and the inhibition of Cd-induced deprivation of tissue Fe by nano-Fe₃O₄ played two key roles in the protective effect of nano-Fe₃O₄ on CdCl₂-induced oxidative damage.