Toxicological interactions of silver nanoparticles and non-essential metals in human hepatocarcinoma cell line

Renata Rank Miranda, Arandi Ginane Bezerra, Ciro Alberto Oliveira Ribeiro, Marco Antônio Ferreira Randi, Carmen Lúcia Voigt, Lilian Skytte, Kaare Lund Rasmussen, Frank Kjeldsen, Francisco Filipak Neto

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Toxicological interaction represents a challenge to toxicology, particularly for novel contaminants. There are no data whether silver nanoparticles (AgNPs), present in a wide variety of products, can interact and modulate the toxicity of ubiquitous contaminants, such as nonessential metals. In the current study, we investigated the toxicological interactions of AgNP (size = 1–2 nm; zeta potential = − 23 mV), cadmium and mercury in human hepatoma HepG2 cells. The results indicated that the co-exposures led to toxicological interactions, with AgNP + Cd being more toxic than AgNP + Hg. Early (2–4 h) increases of ROS (DCF assay) and mitochondrial O 2[rad] levels (Mitosox® assay) were observed in the cells co-exposed to AgNP + Cd/Hg, in comparison to control and individual contaminants, but the effect was partially reverted in AgNP + Hg at the end of 24 h-exposure. In addition, decreases of mitochondrial metabolism (MTT), cell viability (neutral red uptake assay), cell proliferation (crystal violet assay) and ABC-transporters activity (rhodamine accumulation assay) were also more pronounced in the co-exposure groups. Foremost, co-exposure to AgNP and metals potentiated cell death (mainly by necrosis) and Hg 2 + (but not Cd 2 +) intracellular levels (ICP-MS). Therefore, toxicological interactions seem to increase the toxicity of AgNP, cadmium and mercury.

Original languageEnglish
JournalToxicology in Vitro
Pages (from-to)134–143
Publication statusPublished - 2017


  • Cadmium
  • Co-exposure
  • HepG2
  • Interaction
  • Mercury
  • Silver nanoparticles


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