title: Toxicological interactions of silver nanoparticles and non-essential metals in human hepatocarcinoma cell line.
abstract: 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=1-2nm; zeta potential=-23mV), 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 (2-4h) increases of ROS (DCF assay) and mitochondrial O2-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 24h-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 Hg2+(but not Cd2+) intracellular levels (ICP-MS). Therefore, toxicological interactions seem to increase the toxicity of AgNP, cadmium and mercury.
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, CEP 81.531-980, Curitiba, PR, Brazil. Electronic address: renatam.bio@gmail.com.
authors.forename: Renata Rank
authors.initials: RR
authors.lastname: Miranda
authors.affiliation: Departamento de Física, Universidade Tecnológica Federal do Paraná, DAFIS, CEP 80.230-901, Curitiba, PR, Brazil.
authors.forename: Arandi Ginane
authors.initials: AG
authors.lastname: Bezerra
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, CEP 81.531-980, Curitiba, PR, Brazil.
authors.forename: Ciro Alberto
authors.initials: CA
authors.lastname: Oliveira Ribeiro
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, CEP 81.531-980, Curitiba, PR, Brazil.
authors.forename: Marco Antônio Ferreira
authors.initials: MA
authors.lastname: Randi
authors.affiliation: Universidade Estadual de Ponta Grossa, Programa Associado de Pós-Graduação em Química, Setor de Ciências Exatas e Naturais, CEP 84.030-900 Ponta Grossa, PR, Brazil.
authors.forename: Carmen Lúcia
authors.initials: CL
authors.lastname: Voigt
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Lilian
authors.initials: L
authors.lastname: Skytte
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Kaare Lund
authors.initials: KL
authors.lastname: Rasmussen
authors.affiliation: Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Kjeldsen
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, CEP 81.531-980, Curitiba, PR, Brazil. Electronic address: filipak@ufpr.br.
authors.forename: Francisco
authors.initials: F
authors.lastname: Filipak Neto
mesh_terms: D002104:Cadmium / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D056945:Hep G2 Cells; D006801:Humans; D008628:Mercury / Q000633:toxicity*; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D002104:Cadmium; D012834:Silver; D008628:Mercury
keywords: Cadmium; Co-exposure; HepG2; Interaction; Mercury; Silver nanoparticles