A Contrast Examination of Proinflammatory Effects on Kidney Function for γ-Fe2O3 NP and Gadolinium Dimeglumine

Int J Nanomedicine. 2021 Mar 18:16:2271-2282. doi: 10.2147/IJN.S299004. eCollection 2021.

Abstract

Background: Contrast-enhanced magnetic resonance imaging (MRI) is a powerful diagnostic tool for many diseases. In many situations, the contrasts are repeatedly administrated in order to monitor and assess the disease progression.

Objective: To investigate and compare the biological effects of γ-Fe2O3 nanoparticle (NP) and gadolinium dimeglumine (Gd-DTPA) with high and multiple doses on the kidney of healthy mice.

Methods: Polydextrose sorbitol carboxymethyl ether coated γ-Fe2O3 NP with hydrodynamic size of 68.2 nm and clinically applied Gd-DTPA were employed on healthy mice with the repeatedly intravenous administration of high doses. The cell viability of human umbilical vein endothelial cells (HUVEC) in high doses of these two contrast agents were measured using the xCELLigence Real-Time Cell Analysis (RTCA) S16 Instrument. The biological effects of γ-Fe2O3 NP and Gd-DTPA on the kidney were obtained using a biochemical automatic analyzer and multiple proinflammatory factor kit on the serum. Histopathological and immunohistochemistry analysis were taken on kidney tissues.

Results: It showed that the proinflammatory responses elicited by the γ-Fe2O3 NPs were weaker than that by Gd-DTPA, evidenced by the relatively much lower level of IL-1β, IL-6, IL-18, TNF-α, C-reactive protein (CRP) and Ferritin. At the same time, the γ-Fe2O3 NPs did not have the biochemical index elevated, while the Gd-DTPA did.

Conclusion: The γ-Fe2O3 NPs induced weaker proinflammatory effects in reference to the Gd-DTPA, indicating better renal safety. Therefore, it is suggested that γ-Fe2O3 NPs should be safer and optional choice when repeated contrast-enhanced MRI is necessary.

Keywords: cytokines; iron oxide nanoparticles; proinflammatory; renal function.

MeSH terms

  • Animals
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cell Proliferation
  • Cell Survival
  • Contrast Media / chemistry*
  • Ferric Compounds / chemistry*
  • Ferritins / blood
  • Gadolinium DTPA / chemistry*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation / pathology*
  • Kidney / pathology
  • Kidney / physiopathology*
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Nanoparticles / chemistry*
  • Spectrometry, X-Ray Emission
  • Transforming Growth Factor beta / metabolism

Substances

  • Biomarkers
  • Contrast Media
  • Ferric Compounds
  • Transforming Growth Factor beta
  • ferric oxide
  • C-Reactive Protein
  • Ferritins
  • Gadolinium DTPA