Effects of Silver Nanoparticles on the Liver and Hepatocytes In Vitro

Abstract

With the increasing use and incorporation of nanoparticles (NPs) into consumer products, screening for potential toxicity is necessary to ensure customer safety. NPs have been shown to translocate to the bloodstream following inhalation and ingestion, and such studies demonstrate that the liver is an important organ for accumulation. Silver (Ag) NPs are highly relevant for human exposure due to their use in food contact materials, dietary supplements, and antibacterial wound treatments. Due to the large number of different NPs already used in various products and being developed for new applications, it is essential that relevant, quick, and cheap methods of in vitro risk assessment suitable for these new materials are established. Therefore, this study used a simple hepatocytes model combined with an in vivo injection model to simulate the passage of a small amount of NPs into the bloodstream following exposure, e.g., via ingestion or inhalation, and examined the potential of Ag NPs of 20 nm diameter to cause toxicity, inflammation, and oxidative stress in the liver following in vivo exposures of female Wistar rats via iv injection to 50 μg of NPs and in vitro exposures using the human hepatocyte cell line C3A. We found that Ag NPs were highly cytotoxic to hepatocytes (LC(50) lactate dehydrogenase: 2.5 μg/cm(2)) and affected hepatocyte homeostasis by reducing albumin release. At sublethal concentrations with normal cell or tissue morphology, Ag NPs were detected in cytoplasm and nuclei of hepatocytes. We observed similar effects of Ag NPs on inflammatory mediator expression in vitro and in vivo with increase of interleukin-8 (IL-8)/macrophage inflammatory protein 2, IL-1RI, and tumor necrosis factor-α expression in both models and increased IL-8 protein release in vitro. This article presents evidence of the potential toxicity and inflammogenic potential of Ag NPs in the liver following ingestion. In addition, the similarities between in vitro and in vivo responses are striking and encouraging for future reduction, refinement, and replacement of animal studies by the use of hepatocyte cell lines in particle risk assessment.

Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

“…40 Of note, AgNPs cause inflammation in other cell types, such as liver cells both in vivo and in vitro. 41,42 In conclusion, we have shown that co-exposure of gingival fibroblasts to AgNPs and F amplifies the noxious effects of the individual xenobiotics. The mechanism of this action may depend on increased generation of ROS or lipid peroxidation along with a decrease in TAC that could lead to cell death and inflammation.…”

Toxic effects of silver nanoparticles in mammals – does a risk of neurotoxicity exist?

“…Among the oxidative stress-related changes caused by AgNPs, depletion of reduced glutathione (GSH) has been observed in human skin carcinoma cells [6], rat liver cells [60], mouse macrophage cells [100], human liver cells [106,141] and mouse embryonic fibroblasts [74]. Results of studies on aquatic organisms strongly support these in vitro observations [3,38,86], whereas limited in vivo studies demonstrate a lack of changes in GSH levels in liver of exposed rodents [32,39].…”

A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials

“…Studies show that particles with cationic or anionic surface charges are more attractive to phagocytes than neutral particles (Ayala et al, 2013) and it is known that particles below 200 nm in diameter show poor uptake by macrophages in comparison to particles between 0.5 and 3 mm (Desjardins & Griffiths, 2003). Several groups have used in vitro cell models to evaluate NP toxicity either in monocultures (Fisichella et al, 2012;Gaiser et al, 2012Gaiser et al, , 2013Koeneman et al, 2010) or in co-cultures (Muller et al, 2010;RothenRutishauser et al, 2008). Indeed, in vitro models containing two or more types of cells, able to interact with each other and with nanomaterials, seem more able to capture the complexity of the in vivo system.…”