Gold nanoparticles uptake and cytotoxicity assessed on rat liver precision-cut slices

Abstract

Received July 8, 2011; accepted April 13, 2012. A major obstacle in the field of nanotoxicology is the development of an in vitro model that accurately predicts an in vivo response. To address this concern, rat liver precision-cut slices were used to assess the impact of 5-nm gold nanoparticles (GNPs) coated with polyvinylpyrrolidone (PVP) on the mammalian liver, following exposure to different concentrations and for a duration of up to 24 h. The presence of GNPs inside endocytotic vesicles of hepatocytes was appreciable within 30 min of their addition. After 2 h, GNPs were clearly visualized inside endosome-like vesicles within the slice, not only in hepatocytes but also in endothelial and Kupffer cells located within the first two cellular layers. This uptake did not translate into modifications of either phase I or phase II of 7-ethoxycoumarin metabolism or alter activities of cytochrome P450 toward marker substrates. Furthermore, although the GNPs were rapidly internalized, no overt signs of cytotoxicity, assessed through lactate dehydrogenase release, reduction of methylthiazolyldiphenyl tetrazolium bromide, and glutathione levels, were observed. In conclusion, the use of rat liver slices successfully enhanced nanomaterial screening and determined that PVP-coated 5-nm GNPs were biocompatible with rat liver cells. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.