Coexposed nanoparticulate Ag alleviates the acute toxicity induced by ionic Ag⁺in vivo

Health concerns of silver nanoparticles (AgNPs) emerged with the increase of their industrial and biomedical application and thus human exposure. The highly dynamic properties of AgNPs lead to coexposure to nanoparticulate and ionic silver, and the combined effects of different Ag species might alter their individual toxicity. Herein, the toxicity of AgNPs combined with ionic Ag⁺ toward the rat was investigated after intravenous (i.v.) exposure to either AgNPs (5 mg/kg), Ag⁺ (5 mg/kg), or a mixture of Ag⁺ and AgNPs (5 mg/kg for both). Comparable results by histopathological and biochemical studies revealed that the exposure to individual AgNPs causes no apparent toxicity in rats, while Ag⁺ ions at the same dose induced marked acute toxicity. More importantly, while there was a negligible combined effect on the Ag accumulation, the less toxic AgNPs ameliorated Ag⁺ induced toxicity to rat organs after coexposure to the mixture of Ag⁺ and AgNPs, which might result from the complexation of Ag⁺ with the thiols like metallothioneins. Therefore, the combined toxicity of particulate and ionic Ag was complicated by their individual toxicities and also their interaction with intracellular detoxification biomolecules, regardless of differences in Ag accumulation. Although further investigations are still needed for the potential toxic mechanisms of the coexposed AgNPs and Ag⁺, considerations of the combined toxicity of different Ag species will reflect more accurate assessments of their health impacts.