The influence of five metallic nanoparticles on the expression of major drug-metabolizing enzyme genes with correlation of inflammation in mouse livers

Environ Toxicol Pharmacol. 2020 Nov:80:103449. doi: 10.1016/j.etap.2020.103449. Epub 2020 Jun 25.

Abstract

Metallic nanoparticles (NPs) are widely used in medical preparations. The present study aims to find out the influence of widely used five metallic NPs on the expression of major hepatic drug-metabolizing enzyme (DME) genes. Six groups of BALB/C mice, 7 mice each, were exposed to: Gold NPs, silver NPs, copper oxide NPs, silicon dioxide NPs and zinc oxide NPs, for 21 days. Liver biopsies from all mice were subjected to mouse cyp3a11, cyp2c29, ugt2b1 and interleukin-6 (il6) gene expression quantification using real-time polymerase chain reaction, in addition to inflammatory cell infiltration examination. All tested NPs caused a sharp and significant (ANOVA, p value <0.05) downregulation in the expression of DME genes, with the highest influence was observed in mice exposed to copper oxide NPs. Additionally, all NPs induced hepatic inflammation and upregulated the expression of il6 gene, which were inversely correlated with the expression of DMEs. It is concluded that all tested NPs downregulated the expression of DME genes, with the highest influence exhibited by copper oxide NPs, in correlation with inflammation and il6 gene induction in the liver. Further studies are needed to find out the effect of anti-inflammatory compounds against the alterations induced by metallic NPs exposure on hepatic DMEs.

Keywords: Drug metabolizing enzymes; Gene expression; Interleukin 6; Liver; Nanobiology; Nanoparticles.

MeSH terms

  • Animals
  • Cytochrome P-450 CYP2C9 / genetics*
  • Cytochrome P-450 CYP3A / genetics*
  • Down-Regulation
  • Environmental Pollutants / pharmacokinetics
  • Environmental Pollutants / toxicity*
  • Gene Expression / drug effects*
  • Inflammation
  • Interleukin-6 / genetics
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / immunology
  • Liver / pathology
  • Male
  • Metabolic Clearance Rate / genetics
  • Metal Nanoparticles / toxicity*
  • Mice, Inbred BALB C

Substances

  • Environmental Pollutants
  • Interleukin-6
  • interleukin-6, mouse
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP3A
  • cytochrome P450 3A4, mouse