Chapter 19 - Titanium dioxide nanoparticle-induced cytotoxicity and genotoxicity—Generation of reactive oxygen species and cell damage

Abstract

The toxic impact of titanium dioxide nanoparticles (TiO2NPs) on human health is of prime importance because of their wide use in many commercial industries. However, the effect of TiO2NP on liver metabolic function has not been reported. In this chapter, the effect of different doses and exposure time durations of TiO2NPs (21nm) (nano-TiO2) inducing oxidative stress, biochemical disturbance, histological alteration, and cytogenetic aberration in mice liver and bone marrow is investigated. We determine the phototoxicity of nano-TiO2 with different molecular sizes and crystal forms (anatase and rutile) in human skin keratinocytes under UVA irradiation. It has been shown that all nano-TiO2 particles cause phototoxicity, as determined by the MTS assay and by cell membrane damage measured by the lactate dehydrogenase assay, both of which were UVA dose and nano-TiO2 dose dependent. The smaller the particle size of the nano-TiO2, the higher the cell damage. The rutile form of nano-TiO2 showed less phototoxicity than anatase nano-TiO2. The level of photocytotoxicity and cell membrane damage is mainly dependent on the level of reactive oxygen species (ROS) production. Using polyunsaturated lipids in plasma membranes and human serum albumin as model targets, and employing electron spin resonance oximetry and immuno-spin trapping as unique probing methods, we demonstrated that UVA irradiation of nano-TiO2 can induce significant cell damage, mediated by lipid and protein peroxidation. These overall results suggest that nano-TiO2 is phototoxic to human skin keratinocytes, and that this phototoxicity is mediated by ROS generated during UVA irradiation. In conclusion, the selected biochemical parameters and the liver architectures were influenced with dose and time of TiO2NP toxicity, while the genetic disturbance started at the high dose of exposure and for a long duration. Further studies are needed to fulfill the effect of TiO2NPs on pharmaceutical and nutritional applications.