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

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:

• antitoxic effect
• iron oxide nanoparticles
• quercetin
• PC12 cells

Supplementary material

Figure S1 The study of the Qu and QNPs solubility and H₂O₂ cytotoxicity. (A) The comparison of Qu and QNPs solubility as soon as dissolved in water; and (B) three minutes after dissolution; shows that conjugation of Qu to DNPs couldn’t increase its solubility. (C) The MTT assay results of incubating PC12 cells with different concentrations of H₂O₂ for 2 h indicates the dose-dependently cytotoxicity of H₂O₂. ***p<0.001; ****p<0.0001; n=3; mean ± SEM

Acknowledgments

We thank our colleagues for their association and helpful discussions in this study.

Abbreviation list

CAT, catalase activity; DLS, dynamic light scattering; DNPs, Dextran-coated iron oxide nanoparticles; DRSA, DPPH radical scavenging activity; EDX, dispersive X-ray analysis; FE-SEM, field emission-scanning electron microscope; FTIR, Fourier transform infrared; ICP-OES, inductively coupled plasma-optical emission spectrometer; IL, interleukin; iNOS, inducible nitric oxide synthase; IONPs, iron oxide nanoparticles; MPP, 1-methyl-4-phenylpyridinium; NGF, nerve growth factor; PEG, polyethylene glycol; QNPs, Quercetin-conjugated iron oxide nanoparticles; Qu, Quercetin; TAC, total antioxidant capacity; TNF-α, tumor necrosis factor-alpha; XRD, X-ray diffraction.

Availability of data and materials

All of the data and references that we used in this manuscript are available upon request to the corresponding author.

Disclosure

The authors report no conflicts of interest in this work.