Gold nanoparticles administration induced prominent inflammatory, central vein intima disruption, fatty change and Kupffer cells hyperplasia

Abstract

Background: Advances in nanotechnology have identified promising candidates for many biological, biomedical and biomedicine applications. They are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the effects of administration of gold nanoparticles (GNPs) on inflammatory cells infiltration, central vein intima disruption, fatty change, and Kupffer cells hyperplasia in the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use.

Methods: A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of 10, 20 and 50 nm GNPs for 3 or 7 days. Animals were randomly divided into groups, 12 GNPs-treated rats groups and one control group (NG). Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days), size 20 nm (3 or 7 days) and 50 nm (3 or 7 days), respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively.

Results: In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and sinusoids. The alterations in the hepatocytes were mainly vacuolar to hydropic degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis. In addition, inflammatory cell infiltration, Kupffer cells hyperplasia, central veins intima disruption, hepatic strands dilatation and occasional fatty change together with a loss of normal architechiture of hepatic strands were also seen.

Conclusions: The alterations induced by the administration of GNPs were size-dependent with smaller ones induced more affects and related with time exposure of GNPs. These alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These histological alterations may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS) generation which in turn may induce stress in the hepatocytes to undergo necrosis.

Figure 1

GNPs-treated rat received 50 μl of 10 nm particles for 3 days demonstrating hepatocytes cloudy swelling.

Figure 2

GNPs-treated rat received 50 μl of 10 nm particles for 7 days demonstrating Kupffer cells hyperplasia.

Figure 3

GNPs-treated rat received 50 μl of 10 nm particles for 3 days demonstrating necrotic hepatocytes.

Figure 4

GNPs-treated rat received 100 μl of 10 nm particles for 3 days demonstrating inflammatory cell infiltration.

Figure 5

GNPs-treated rat received 100 μl of 10 nm particles for 7 days demonstrating hepatic fatty degeneration.

Figure 6

GNPs-treated rat received 50 μl of 20 nm particles for 7 days demonstrating hepatic central vein intima disruption.

Figure 7

GNPs-normal rat demonstrating normal hepatocytes.