In vivo investigation on the chronic hepatotoxicity induced by intraperitoneal administration of 10-nm silicon dioxide nanoparticles

Abstract

Background: Silicon dioxide (silica) nanoparticles (SDNPs) are widely used in nanotechnology and medicine, but these nanomaterials may carry a high risk for human health while little is known about their toxicity.

Methods: We investigated the alterations in morphometry, biochemistry, hematology, histology of liver tissue and gene expression of drug-metabolizing enzymes induced by 10-nm SDNPs. Healthy male Wistar albino rats were exposed to 20, 35 and 50 repeated injections of SDNPs (2 mg/kg body weight). Whole blood, serum and plasma samples were used for hematological and biochemical analyses, whereas liver biopsies were processed for histopathological and gene expression alterations.

Results: In comparison with control rats, exposure to SDNPs lowered the body weight gain and liver index and increased the counts of white blood cells and platelets, but lowered the platelet larger cell ratio and plateletcrit. Levels of alkaline phosphatase, lactate dehydrogenase, low-density lipids, procalcitonin, aspartate aminotransferase and alanine aminotransferase, as well as potassium, phosphorus and iron concentrations, were increased. Histopathology revealed that SDNPs could induce hydropic degeneration, sinusoidal dilatation, hyperplasia of Kupffer cells, karyopyknosis and infiltration of inflammatory cells in the liver. SDNPs reduced the expression of 12 genes of drug-metabolizing enzymes significantly (p<0.05).

Conclusion: These results suggest that SDNPs could cause alterations in morphometry, biochemistry, hematology, liver tissues and the expression of drug-metabolizing enzyme genes.

Keywords: biochemical alterations; gene expression; hematological alterations; histological alterations; morphometric alterations; toxicity.

Figure 1

Effect of SDNPs on body weight: twice-weekly changes in body weight gain with the number of SDNP injections. Notes: *A significant difference (Student’s t-test, p<0.05) in comparison with the body weight gain of control rats. The decrease in the body weight gain of SDNP-treated rats in comparison with control rats is shown. Abbreviations: SDNPs, silicon dioxide nanoparticles; w, week.

Figure 2

Change in the liver index in correlation with the number of SDNP injections. Note: The decrease in the liver index is directly proportional to the number of SDNP injections received by experimental rats. Abbreviations: SDNPs, silicon dioxide nanoparticles; inj, injections.

Figure 3

Analyses of biochemical alterations induced by 20, 35 and 50 injections of 10-nm SDNPs (2 mg/kg body weight). Note: *A significant difference (p-value, Student’s t-test) in comparison with the control group. Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HDL, high-density lipid; LDH, lactate dehydrogenase; SDNPs, silicon dioxide nanoparticles; inj, injections.

Figure 4

Analyses of hematological alterations induced by 20, 35 and 50 injections of 10-nm SDNPs (2 mg/kg body weight). Note: *A significant difference (p-value, Student’s t-test) in comparison with the control group. Abbreviations: P-LCR, platelet larger cell ratio; SDNPs, silicon dioxide nanoparticles; WBCs, white blood cells; inj, injections.

Figure 5

Microphotograph sections of the liver of control rats (A and B) and rats subjected to 50 injections of 10-nm SDNPs (C–H), stained by H&E. Notes: (A) In control rats, the hepatic architecture demonstrates intact hepatic strands radiating outward from a central vein. (B) In control rats, hepatocytes display eosinophilic cytoplasm separated by vascular channels. The round nuclei dispersing smooth chromatin are shown. (C) Hydropic degeneration demonstrating swelling and cytoplasmic vacuolization. (D) Karyopyknosis showing nuclei shrinkage and chromatin condensation. (E) Infiltration of inflammatory cells demonstrating aggregation of inflammatory cells in the hepatic portal space. (F) Infiltration of lobular inflammatory cells (mainly lymphocytes) in the lobular hepatic strands. (G) Hyperplasia of Kupffer cells showing enlargement and hypertrophy of these defense cells. (H) Sinusoidal dilatation exhibiting widening of the capillaries lining the hepatic strands. Abbreviations: H&E, with hematoxylin and eosin; SDNPs, silicon dioxide nanoparticles.