In vivo investigation on the chronic hepatotoxicity induced by intraperitoneal administration of 10-nm silicon dioxide nanoparticles

Int J Nanomedicine. 2018 May 7:13:2685-2696. doi: 10.2147/IJN.S162847. eCollection 2018.

Abstract

Background: Silicon dioxide (silica) nanoparticles (SDNPs) are widely used in nanotechnology and medicine, but these nanomaterials may carry a high risk for human health while little is known about their toxicity.

Methods: We investigated the alterations in morphometry, biochemistry, hematology, histology of liver tissue and gene expression of drug-metabolizing enzymes induced by 10-nm SDNPs. Healthy male Wistar albino rats were exposed to 20, 35 and 50 repeated injections of SDNPs (2 mg/kg body weight). Whole blood, serum and plasma samples were used for hematological and biochemical analyses, whereas liver biopsies were processed for histopathological and gene expression alterations.

Results: In comparison with control rats, exposure to SDNPs lowered the body weight gain and liver index and increased the counts of white blood cells and platelets, but lowered the platelet larger cell ratio and plateletcrit. Levels of alkaline phosphatase, lactate dehydrogenase, low-density lipids, procalcitonin, aspartate aminotransferase and alanine aminotransferase, as well as potassium, phosphorus and iron concentrations, were increased. Histopathology revealed that SDNPs could induce hydropic degeneration, sinusoidal dilatation, hyperplasia of Kupffer cells, karyopyknosis and infiltration of inflammatory cells in the liver. SDNPs reduced the expression of 12 genes of drug-metabolizing enzymes significantly (p<0.05).

Conclusion: These results suggest that SDNPs could cause alterations in morphometry, biochemistry, hematology, liver tissues and the expression of drug-metabolizing enzyme genes.

Keywords: biochemical alterations; gene expression; hematological alterations; histological alterations; morphometric alterations; toxicity.

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / metabolism
  • Animals
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / etiology*
  • Gene Expression Regulation / drug effects
  • Hyperplasia / chemically induced
  • Hyperplasia / pathology
  • Inactivation, Metabolic / drug effects
  • Inactivation, Metabolic / physiology
  • Injections, Intraperitoneal
  • Kupffer Cells / pathology
  • L-Lactate Dehydrogenase / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Rats, Wistar
  • Silicon Dioxide / administration & dosage
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / toxicity*

Substances

  • Silicon Dioxide
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase