The antitoxic effects of quercetin and quercetin-conjugated iron oxide nanoparticles (QNPs) against H2O2-induced toxicity in PC12 cells

Int J Nanomedicine. 2019 Aug 26:14:6813-6830. doi: 10.2147/IJN.S212582. eCollection 2019.

Abstract

Background: We recently showed that quercetin-conjugated iron oxide nanoparticles (QNPs) promoted the bioavailability of quercetin (Qu) in the brain of rats and improved the learning and memory of diabetic rats. In this study, we characterized the modifications in the antitoxic effects of Qu after conjugation.

Materials and methods: We conjugated Qu to dextran-coated iron oxide nanoparticles (DNPs) and characterized DNPs and QNPs using FTIR, XRD, DLS, Fe-SEM, and EDX analyzes. The antiradical properties of Qu, DNPs, and QNPs were compared by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity assay. Catalase-like activities of DNPs and QNPs were estimated using catalase activity assay kit, and the antitoxic effects of Qu and QNPs were evaluated with spectrophotometry, MTT assay, flow cytometry, and real-time q-PCR.

Results: Qu had a stronger anti-radical activity than DNPs and its activity decreased after being conjugated to DNPs. The catalase-like activity of DNPs remained intact after conjugation. DNPs had less toxicity on PC12 cells viabilities as compared to free Qu, and the conjugation of Qu with DNPs attenuated its cytotoxicity. Furthermore, MTT assay results indicated 24 h pretreatment with Qu had more protective effects than QNPs against H2O2-induced cytotoxicity, while Qu and QNPs had the same effects for 48 and 72 h incubation. Although the total antioxidant capacity of Qu was attenuated after conjugation, the results of flow cytometry and real-time q-PCR confirmed that 24 h pretreatment with the low concentrations of Qu and QNPs had the similar antioxidant, anti-inflammatory, and anti-apoptotic effects against the cytotoxicity of H2O2.

Conclusion: Qu and QNPs showed the similar protective activities against H2O2-induced toxicity in PC12 cells. Given the fact that QNPs have magnetic properties, they may serve as suitable carriers to be used in neural research and treatment.

Keywords: PC12 cells; antitoxic effect; iron oxide nanoparticles; quercetin.

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacokinetics
  • Antioxidants / pharmacology*
  • Catalase / pharmacology
  • Dextrans / chemistry
  • Drug Liberation
  • Ferric Compounds / chemistry*
  • Ferric Compounds / pharmacology
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Hydrogen Peroxide / toxicity*
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / therapeutic use*
  • PC12 Cells
  • Quercetin / chemistry
  • Quercetin / pharmacokinetics
  • Quercetin / pharmacology*
  • Rats
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Antioxidants
  • Dextrans
  • Ferric Compounds
  • Free Radical Scavengers
  • ferric oxide
  • Quercetin
  • Hydrogen Peroxide
  • Catalase