title: 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.
authors.affiliation: Department of Physics and Astronomy, College of Science, King Saud University, Saudi Arabia. abdelhalimmak@yahoo.com
authors.forename: Mohamed Anwar K
authors.initials: MA
authors.lastname: Abdelhalim
authors.forename: Bashir M
authors.initials: BM
authors.lastname: Jarrar
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D002843:Chromatin / Q000187:drug effects / Q000473:pathology; D003593:Cytoplasm / Q000187:drug effects / Q000473:pathology; D004108:Dilatation, Pathologic / Q000139:chemically induced / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D006818:Hyalin / Q000187:drug effects*; D007263:Infusions, Parenteral; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D009336:Necrosis / Q000139:chemically induced; D010316:Particle Size; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D014617:Vacuoles / Q000187:drug effects* / Q000473:pathology
chemical_list: D002843:Chromatin; D006046:Gold