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

Abstract

BackgroundNanoparticles (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.MethodsA 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.ResultsIn 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.ConclusionsThe 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.

Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles

“…15,16 In contrast, monodispersed Au NPs did not exert a higher acute effect compared to their agglomerates, when using pulmonary inflammation as a marker for toxicity after intratracheal instillation in rats. 17 Furthermore, the model organism Drosophila melanogaster showed DNA fragmentation and significant concentration-dependent and size-independent modulation of expression levels of the genes involved in stress stimuli (hsp70 and hsp83), DNA damage (p53) and apoptosis pathway (Dark, Dronc, and Dredd) upon ingestion of Au NPs.…”

“…Notes: Mass concentrations (0.1-100 µg/ml) were expressed as theoretically calculated number of au NPs ranging from 2.93×10 12 to 7.92×10 16 . In PBl (A and C) and raw264.7 (B and D), after 2 hours (A and B) and 24 hours (C and D) treatment, no statistically significant differences among the cytotoxicity of 5 nm and 15 nm au NPs were observed.…”

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

“…[27][28][29][30][31][32] However, little attention has been paid to kidneys, which are particularly susceptible to xenobiotics due to their high blood supply and ability to concentrate toxins. Sereemaspun et al 33 demonstrated that GNPs were heavily taken up by kidney cells, causing nephrotoxicity.…”

Evaluation of the Effects of Aluminum Phosphate and Calcium Phosphate Nanoparticles as Adjuvants in Vaccinated Mice

“…The swelling of hepatocytes might be exhibited as a result of disturbances of membranes function, that could be confirmed by the accompanied leakage of lysosomal hydrolytic enzymes [22]. The hydropic degeneration is a result of ion and fluid homeostasis unbalance that lead to an increase in intracellular water [22]. The histological changes appearing in the kidney of adult and juvenile groups were pronounced in case of alum adjuvant.…”

“…Küpffer cells activation might indicate that nanoparticles activate the phagocytic activity of the sinusoidal cells by increasing the number of Küpffer cells to help in removing the accumulated nanoparticles [21]. The swelling of hepatocytes might be exhibited as a result of disturbances of membranes function, that could be confirmed by the accompanied leakage of lysosomal hydrolytic enzymes [22]. The hydropic degeneration is a result of ion and fluid homeostasis unbalance that lead to an increase in intracellular water [22].…”