Histopathology of the Liver, Kidney, and Spleen of Mice Exposed to Gold Nanoparticles

Abstract

Gold nanoparticles (GNPs) are biocompatible nanomaterials that are currently researched for biomedical applications such as imaging and targeted drug delivery. In this investigation, we studied the effects of a single dose (injected on day 1) as well as a priming dose (two injections with a gap of one week) of 5 nm, 20 nm, and 50 nm diameter GNPs on the structural and biochemical changes in the liver, kidney, and spleen of mice. The results showed that small sized GNPs (5 nm) produced significant pathological changes in the liver on day 2 that gradually reduced on day 8. The medium (20 nm) and large (50 nm) sized GNPs preferentially targeted the spleen and caused significant pathological changes to the spleen architecture on day 2 that persisted on day 8 as well. There were minimal and insignificant pathological changes to the kidneys irrespective of the GNPs size. The animals that were primed with the pre-exposure of GNPs did not show any aggravation of histological changes after the second dose of the same GNPs. None of the dose regimens of the GNPs were able to significantly affect the markers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) in all of the organs that were studied. In conclusion, the size of GNPs plays an important role in their pathological effects on different organs of mice. Moreover, the primed animals become refractory to further pathological changes after the second dose of GNPs, suggesting the importance of a priming dose in medical applications of GNPs.

Keywords: gold nanoparticles; histopathology; kidney; liver; mice; priming dose; spleen.

Figure 1

Evaluation of the size and shape of the GNPs using transmission electron microscopy. Scale bar = 50 nm.

Figure 1

Evaluation of the size and shape of the GNPs using transmission electron microscopy. Scale bar = 50 nm.

Figure 2

Histopathology of the liver. Light micrographs of the liver sections from different treatment groups. The numbers on the images represent the treatment groups according to Table 1. (1) Control mouse liver section showing normal hepatic architecture, (2) marked pathological changes characterized by steatosis and the abundance of micro and macro vesicles, (3) and (4) look healthy with normal hepatocytes while some bi-nucleated cells refer to regeneration, (5) cytoplasmic degeneration and some aggregation of inflammatory cells, (6) looks healthy with mild activation of Kupffer cells, (7) multi necrotic foci filled with hemorrhage and also the presence of infiltrative cells, (8) necrotic foci filled with edema and surrounded by inflammatory cells, (9) and (10) look healthy with bi-nucleated cells and the activation of Kupffer cells. The bar graph shows the scoring of the pathological changes. * p < 0.05 and ** p < 0.01 versus the control group using Dunnett’s multiple comparison test. (Magnification 200×).

Figure 3

Histopathology of the kidney. Light micrographs of the kidney sections from the different treatment groups. The numbers on the images represent the treatment groups according to Table 1. (1) Control kidney section showing normal renal cortex and glomerular tufts, (2), (3), and (4) diminished and distorted glomeruli, (5) leukocyte infiltration, edema exudate, and necrotic foci, (6) distorted glomeruli, (7) relatively healthy glomeruli and tubules, (8) diminished and distorted glomeruli and dilated tubules, (9) relatively healthy glomerulus with abundant capsular space, (10) infiltration of inflammatory cells surrounding the distorted glomeruli and tubules. The bar graph shows the scoring of the pathological changes. (Magnification 200×).

Figure 4

Histopathology of the spleen. Light micrographs of the spleen sections from the different treatment groups. The numbers on the images represent the treatment groups according to Table 1. (1) Control spleen section showing normal splenic architecture with normal lymphoid follicles and sinuses, (2) well-defined spleen section, (3) minimized lymphoid follicles, but still the white pulp is more well-defined than the red pulp, (4) ill-defined spleen section with diffuse white pulp, distorted lymphoid architecture, and giant macrophages, (5) well-defined spleen section with a healthy lymphoid follicle, (6) ill-defined spleen section, (7) lymphoid follicles surrounded by giant macrophages, (8) well-defined spleen section, (9) presence of granular leukocytes in between lymphocytes in lymphoid follicles besides giant macrophages, (10) presence of giant macrophages. The bar graph shows the scoring of the pathological changes. * p < 0.05 and ** p < 0.01 versus the control group using Dunnett’s multiple comparison test. (Magnification 200×).