Titanium Dioxide Nanoparticles Increase Superoxide Anion Production by Acting on NADPH Oxidase

Abstract

Titanium dioxide (TiO2) anatase nanoparticles (NPs) are metal oxide NPs commercialized for several uses of everyday life. However their toxicity has been poorly investigated. Cellular internalization of NPs has been shown to activate macrophages and neutrophils that contribute to superoxide anion production by the NADPH oxidase complex. Transmission electron micrososcopy images showed that the membrane fractions were close to the NPs while fluorescence indicated an interaction between NPs and cytosolic proteins. Using a cell-free system, we have investigated the influence of TiO2 NPs on the behavior of the NADPH oxidase. In the absence of the classical activator molecules of the enzyme (arachidonic acid) but in the presence of TiO2 NPs, no production of superoxide ions could be detected indicating that TiO2 NPs were unable to activate by themselves the complex. However once the NADPH oxidase was activated (i.e., by arachidonic acid), the rate of superoxide anion production went up to 140% of its value without NPs, this effect being dependent on their concentration. In the presence of TiO2 nanoparticles, the NADPH oxidase produces more superoxide ions, hence induces higher oxidative stress. This hyper-activation and the subsequent increase in ROS production by TiO2 NPs could participate to the oxidative stress development.

Effects of titanium dioxide nanoparticles on human keratinocytes

“…It is known that ROS induction can mediate and regulate caspase-related cell death pathways, specifically Fas-mediated apoptotic cell death that proceeds through the FADD complex pathway by way of caspase 8 activation (Izeradjene et al, 2005; Thornberry & Lazebnik, 1998; Yoo et al, 2012). Specifically, an increase in superoxide production has been repeatedly shown to be a precursor to TiO 2 -induced cell death in various cell lines (Masoud et al, 2015; Niska et al, 2015). It is feasible that the reason ROS scavengers used in Figure 3 had no effect on TiO 2 -induced apoptosis in HaCaTs is because of the difference in time points used to analyze apoptosis in Figure 3 (12 and 24 h) versus ROS production in Figure 1 (15 and 30 min, 1 h).…”

Sequential assessment via daphnia and zebrafish for systematic toxicity screening of heterogeneous substances

“…Rather than focusing on the characteristics of each substance, this study focused on the ability of the systematic sequential bioassay for assessing the combined toxic effects of the mixtures (Gao et al, 2013;Grabicova et al, 2013;Masoud et al, 2015;Wang et al, 2016). The Daphnia magna, recommended by the OECD, and the zebrafish transgenic models, both abide by the regulations stated by the OECD while providing the means to efficiently carry out an assessment experiment.…”

In vivo assessment of silver nanoparticle induced reactive oxygen species reveals tissue specific effects on cellular redox status in the nematode Caenorhabditis elegans

“…Furthermore, there is little information on how NPs affect in vivo ROS production in the exposed organisms. In the current study, we capitalized on recent advances in if mitochondrial function is compromised (Masoud et al, 2015, Abdal Dayem et al, 2017, Grzelak et al, 2018. By employing the GA508 SOD-1 reporter strain we were able to firmly demonstrate that NM300K Ag NPs induced sod-1 superoxide antioxidant defense in a dose dependent manner (Figure 3), which unequivocally is a response to elevated cytosolic superoxide (Doonan et al, 2008).…”