SUMMARY
The rapid increasing use of nanoparticles (NPs) in industry, consumer market and nanomedicine in the last decades and the possible environmental accumulation and likelihood of exposure to human beings raised concerns regarding their adverse effects and necessity to search for appropriate protective strategies against their possible nanotoxicity.
The present work dealt with the investigation of the nanotoxicity of different doses and sizes of nickel nanoparticles (NiNPs) in the liver and kidney of rats and the protective role of the antioxidant quercetin (Qu) from the histological, ultrastructural, biochemical and immunohistochemical points of view.
For conducting this work, 72 male Wistar rats were used. Three different doses (5mg/kg, 20mg/kg and 100mg/kg) and three different sizes (20nm, 40nm and 70nm) of NiNPs were intraperitoneally administrated as a suspension in saline solution. For studying the protective role of Qu against NiNPs toxicity, a daily oral dose of 25mg/Kg/B.W. Qu was administrated one hour before NiNPs exposure. All duration time of all experiments was 28 days. The actual NiNPs size was measured using transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques.
As revealed by DLS and TEM the actual size of the NiNPs was approximately similar to the size written by the manufacturers. NiNPs were found to decrease the body weight gain of the rats compared to the control. The histological study revealed various changes in the liver and kidneys of rats following NiNPs administration. The main histopathological features included degenerated hepatic and renal cells and the appearance of inflammatory infiltrated leucocytes.
Biochemically, NiNPs induced oxidative stress elevation through raising the tissue malondialdehyde (MDA) and decreasing the endogenous antioxidants such as superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPX), and catalase (CAT) in comparison to the control. This oxidative stress also affected the liver and renal function markers. The liver function markers included serum alanine aminotransferases and aspartate aminotransferases (ALT and AST respectively) and bilirubin, while the kidney function marker included serum creatinine level.
The main mode of cell death following NiNPs administration was apoptosis and this was confirmed by using immunohistochemical techniques in addition to the TEM technique.
Ultrastructurally, NiNPs directly affected the mitochondria and rough endoplasmic reticulum structure in the liver and kidney. The most ultrastructural feature induced by NiNPs was the altered endoplasmic reticulum and mitochondria structure and intensity compared to the control. The present investigation followed the entry pathway of NiNPs into hepatic and renal cells. Different translocation pathways of NiNPs internalization were suggested but the most obvious one was the endocytic pathway of translocation. Direct diffusion of the NPs was also suggested.
All above mentioned histological, biochemical, immunohistochemical and ultrastructural changes were dose dependent. Furthermore, the particle size was found to affect the toxicity, in which the smaller size showed more toxicity compared to the larger sizes.
Pretreating with Qu, most of these histological, biochemical, immunohistochemical and ultrastructural alterations induced by NiNPs were ameliorated. The antioxidant property of Qu which was confirmed by the present investigation was the main reason behind this protective role. The significant decrease in NiNPs content in the liver and kidney of NiNPs plus Qu treated rats compared to NiNPs group may indicate the chelating property of this bioflavonoid.
The present results concerning the internalization pathway of these NPs into the cells may be very useful in the field of nanomedicine.