) of nanoparticles and their ADME (absorption, distribution, meta

) of nanoparticles and their ADME (absorption, distribution, metabolism and elimination) characteristics is critical to achieve desired biological effect (Li and Huang, 2008 and Liang et al., 2008). Kunzmann et al. (2011) have extensively reviewed the commonly studied nanomaterials viz., iron oxide nanoparticles, dendrimers, mesoporous silica particles, gold nanoparticles, and carbon nanotubes with reference to their toxicity, biocompatibility, biodistribution and biodegradation. The authors re-emphasize the importance of physico-chemical

characteristics of nanoparticles as well as ensuing immunological reactions vis-a-vis the target biological application. Zhi Yong et al. (2009) recommend the use of radiotracer techniques for determining ADME characteristics. When exposed to light or transition metals, nanoparticles Veliparib purchase may promote the formation of pro-oxidants which, in turn, destabilizes the delicate balance between the biological system’s ability to produce and detoxify the reactive oxygen species (ROS) selleck kinase inhibitor (Curtis et al., 2006 and Kabanov, 2006). Size, shape and aggregation are nanomaterial characteristics that can culminate in ROS generation (Shvedova et al., 2005a and Shvedova et al., 2005b). Properties

such as surface coating and solubility may possibly decrease or amplify the size effect as illustrated in Fig. 2. ROS include free radicals such as the superoxide anion (O2 −), hydroxyl radicals (.OH) and the non-radical hydrogen peroxide (H2O2), which are

constantly generated in cells under normal conditions as a consequence of aerobic metabolism. When cells are exposed to any insult (chemical/physical), it Low-density-lipoprotein receptor kinase results in the production of ROS (Luo et al., 2002). But cells are also endowed with an extensive antioxidant defense system to combat ROS, either directly by interception or indirectly through reversal of oxidative damage. Cellular antioxidants can be divided into primary (superoxide dismutase, glutathione peroxidase, catalase and thioredoxin reductase) or secondary defense (reduced glutathione) mechanisms (Stahl et al., 1998). Superoxide dismutase (SOD) converts the highly reactive radical superoxide into the less reactive peroxide (H2O2) which further can be destroyed by catalase or glutathione peroxidase (GPx) (Fridovich, 1995). Catalase is a highly reactive enzyme, which converts H2O2 to form water and molecular oxygen (Mates and Sanchez-Jimenez, 1999). Glutathione peroxidase catalyzes the reduction of a variety of hydroperoxides (ROOH and H2O2) using GSH, thereby protecting mammalian cells against oxidative damage and also reducing cellular lipid hydroperoxides (Jornot et al., 1998). Under normal conditions, more than 95% of the glutathione (GSH) in a cell is reduced and so the intracellular environment is usually highly reducing. However, depletion of GSH will lower the reducing capacity of the cell and can therefore induce oxidative stress without the intervention of ROS.

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