Intraperitoneal injection of magnetic Fe₃O₄-nanoparticle induces hepatic and renal tissue injury via oxidative stress in mice

Abstract

Because of its unique magnetic properties, the iron oxide (Fe₃O₄) nanoparticle has been widely exploited and its application in various fields has promised immense benefits. However, doubts exist over the use of Fe₃O₄-nanoparticles in human beings. Thus, the aim of the current study was to find out the potential safety range of medical use. Twenty-five Kunming mice were exposed to Fe₃O₄-nanoparticles via intraperitoneal injection daily for 1 week at doses of 0, 5, 10, 20, and 40 mg/kg. Hepatic and renal tissues were sliced for physiological observation. Injuries were observed in the high-dose groups (20 and 40 mg/kg) compared with the control group (0 mg/kg). Biomarkers of reactive oxygen species, glutathione, malondialdehyde, DNA-protein crosslinks, and 8-hydroxy-2'-deoxyguanosine in the hepatic and renal tissues were detected. Injury to tissues and oxidative damage to cells at the molecular level was found. The safest dose recommended from the results of this study is 5 mg/kg, as we believe this to be an upper limit balancing the benefits and risks for sub-long-term exposure.

Keywords: 8-hydroxy-2′-deoxyguanosine; DNA-protein crosslinks; Fe3O4-nanoparticles; glutathione; malondialdehyde; reactive oxygen species.

Figure 1

Crystal appearance of Fe₃O₄-nanoparticles (SEM). Abbreviation: SEM, scanning electron microscopy.

Figure 2

Size distribution of Fe₃O₄-nanoparticles dispersed in phosphate-buffered saline.

Figure 3

Zeta potential of Fe₃O₄-nanoparticles.

Figure 4

Liver and renal kidney slices (stained with hematoxylin and eosin). Row (A) presents pictures of Liver slices and Row (B) pictures of Kidney slices.

Figure 5

ROS level of liver and kidney homogenates. (A) presents the data of Liver and (B) the data of Kidney. Notes: Compared with the control group, *indicates 0.01 < P < 0.05, **indicates P < 0.01. Abbreviation: ROS, reactive oxygen species.

Figure 6

Reduced-GSH level of liver and kidney homogenates. (A) presents the data of Liver and (B) the data of Kidney. Notes: Compared with the control group, *indicates 0.01 < P < 0.05, **indicates P < 0.01. Abbreviation: GSH, Glutathione.

Figure 7

MDA level of liver and kidney homogenates. (A) presents the data of Liver and (B) the data of Kidney. Notes: Compared with the control group, *indicates 0.01 < P < 0.05. Abbreviation: MDA, Malondialdehyde.

Figure 8

8-OH-dG level of liver and kidney homogenates. (A) presents the data of Liver and (B) the data of Kidney. Notes: Compared with the control group, *indicates 0.01 < P < 0.05, **indicates P < 0.01. Abbreviation: 8-OH-dG, 8-hydmxy-2′-deoxyguanosine.

Figure 9

DPC coefficient of liver and kidney homogenates. (A) presents the data of Liver and (B) the data of Kidney. Notes: Compared with the control group, *indicates 0.01 < P < 0.05, **indicates P < 0.01. Abbreviation: DPC, DNA-Protein Crosslinks.

Figure 10

Outline of experiment procedures. Abbreviations: 8-OH-dG, 8-hydmxy-2′-deoxyguanosine; DPC, DNA-Protein Crosslinks; MDA, Malondialdehyde; ROS, reactive oxygen species; GSH, Glutathione.

Figure 11

Expected safe dose of Fe₃O₄-nanoparticles for sub-long-term systematic delivery.