Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis in the liver

Abstract

Background: Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. The aim of the present study was to investigate the particle-size, dose and exposure duration effects of gold nanoparticles (GNPs) on the hepatic tissue in an attempt to cover and understand the toxicity and their potential therapeutic and diagnostic use.

Methods: A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days) to investigate particle-size, dose and exposure duration effects of GNPs on the hepatic tissue.

Results: In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly vacuolar to hydropic degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis.

Conclusions: The hepatocytes swelling might be exhibited as a result of disturbances of membranes function that lead to massive influx of water and Na+ due to GNPs effects accompanied by leakage of lysosomal hydrolytic enzymes that lead to cytoplasmic degeneration and macromolecular crowding. Hydropic degeneration is a result of ion and fluid homestasis that lead to an increase of intracellular water. The vacuolated swelling of the cytoplasm of the hepatocytes of the GNPs treated rats might indicate acute and subacute liver injury induced by the GNPs. Binucleation represents a consequence of cell injury and is a sort of chromosomes hyperplasia which is usually seen in regenerating cells. The induced histological 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 alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction 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 atrophy and necrosis. More histomorphologcal, histochemical and ultrastrucural investigations are needed in relation of the application of GNPs with their potential role as a therapeutic and diagnostic tool.

Figure 1

GNPs-normal rat demonstrating normal hepatocytes.

Figure 2

GNPs-treated rat. (A) GNPs-treated rat received 50 μl of 10 nm particles for 3 days demonstrating hepatocytes cloudy swelling. (B) GNPs-treated rat received 100 μl of 10 nm particles for 7 days demonstrating hydropic degeneration. (C) GNPs-treated rat received 50 μl of 10 nm particles for 3 days demonstrating hyaline inclusions. (D) GNPs-treated rat received 100 μl of 10 nm particles for 7 days demonstrating hyaline vacuolation.

Figure 3

GNPs-treated rat. (A) GNPs-treated rat received 100 μl of 50 nm particles for 3 days demonstrating pyknotic hepatocytes. (B) GNPs-treated rat received 100 μl of 50 nm particles for 3 days demonstrating clumping and condensation of the chromatin materials in the periphery of the nuclei together with irregularity nuclear membranes. (C) GNPs-treated rat received 50 μl of 50 nm particles for 7 days demonstrating karyorrhexis. (D) GNPs-treated rat received 100 μl of 50 nm particles for 7 days demonstrating karyolysis.

Figure 4

GNPs-treated rat. (A) GNPs-treated rat received 100 μl of 50 nm particles for 3 days demonstrating binucleation. (B) GNPs-treated rat received 100 μl of 20 nm particles for 7 days demonstrating binucleation.

Figure 5

GNPs-treated rat. (A) GNPs-treated rat received 50 μl of 10 nm particles for 3 days demonstrating necrotic hepatocytes. (B) GNPs-treated rat received 50 μl of 10 nm particles for 3 days demonstrating hepatic sinusoidal dilatation.