الفهرس 
1. INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 121 |  |  |
| | | from | 121 | | |
Abstract
Various NPs exhibit oxidative stress dependent toxicity. Upon NP exposure, ROS generation is capable of inducing oxidative DNA damage, strand breaks, protein denaturation, and lipid peroxidation thereby demonstrating the mutagenic and carcinogenic characteristics associated with nanoparticles (Agarwal et al., 2013).
Excess free radical production leads to mitochondrial membrane damage causing necrosis and cell death. Phagocytes including neutrophils and macrophages generate massive ROS upon incomplete phagocytosis of NP through the NADPH-oxidase enzyme system whereas NP-induced ROS triggers an inflammatory cascade of chemokine and cytokine expression via activation of cell signaling pathways such as MAPK, NF-𝜅B, Akt, and RTK. Furthermore, oxidative stress mediated stimulation of these cellular mechanisms results in transcription of genes responsible for fibrosis, MT, and carcinogenesis.NP-elicited ROS is at the center stage for majority of the ensuing adverse outcomes.
Brunner et al. (2006) added that solubility is an important property that explains the reasons of toxic effects on many organisms.
Because of the NPs have an extremely small size and large surface area to volume ratio; they can easily cross the biological cells and membranes (Vishwakarma et al., 2010). Once inside the body, they can enter the bloodstream and hence reach different organs, including blood cells, liver, spleen, kidney, testis, thymus, heart, lungs and brain that may damage vital functions of the affected organs (Cho et al., 2012; Li et al., 2012).
Several studies have reported that the immune organs are the main sites for the deposition of NPs after systemic exposure, where they encounter a complex net of immune cells and huge number of plasma proteins. Once inside the cell, NPs may induce adverse effects such as enhanced expression of pro-inflammatory cytokines, generation of ROS and DNA strand breaks (Rothen-Rutishauser et al., 2007). Cross et al. (2007) stated that NPs have been known to localize even in the regional lymph nodes when administered dermally. It is highly probable that macrophages carry NPs to the different organs, as their accumulation has been found in the phagolysosomes of tissue residing macrophages (Sadauskas et al., 2007).
Oberdörster (2004) found that different NPs can reach the brain and cause neurological, being associated even with neurodegenerative diseases (Peters et al., 2006; Hu and Gao, 2010). This translocation can happen both directly, through axonal transport from olfactory epithelium, or indirectly by passing to the blood stream and crossing the blood brain barrier.
1.5. Mechanisms of toxicity of nanoparticles
There are several mechanisms explaining the toxicity of nanoparticles:
1. First, nanoparticles are able to interact with biomolecules due to their large specific surface area. During this process, chemical reactions take place and increases of superoxide radical (O2−) formation, which leads to oxidative stress and accumulation reactive oxygen species (ROS) (De Berardis et al., 2010). ROS contain superoxide anions (O2−), hydroxyl radicals, and hydrogen peroxide (H2O2).
Second, it has been reported that NPs with high activity is likely.