Investigation on the mechanism of non‐photocatalytically TiO₂‐induced reactive oxygen species and its significance on cell cycle and morphology

Abstract

Titanium dioxide (TiO2 ) nanoparticles are widely used in daily human life, and were reported to elicit biological effects such as oxidative stress either generating reactive oxygen species (ROS) or causing cell necrosis without generating ROS, whose underlying molecular mechanisms are not yet known. In this study, the role of dissolved oxygen in TiO2 catalytic activity in dark environment, and long-term cytotoxic effects of TiO2 exposure were investigated. To determine the effect of dissolved oxygen, the anatase-TiO2 nanoparticle suspension was prepared both in deoxygenated and regular MilliQ water, and a ~ 9-fold higher ROS in regular MilliQ samples was observed compared to deoxygenated samples while in the dark, which suggested dissolved oxygen as the driving agent behind the TiO2 catalytic reaction. On the other hand, the differential cell viability and endogenous ROS activity was demonstrated through a sensitive macrophage-based assay, on a dose- and time-dependent manner. Both the cell number and endogenous ROS activity increased with increase in time till 48 h, followed by a reduction at 72 h exposure period. Long-term exposures to these nanoparticles even at low concentrations were found detrimental to cells, where late apoptosis until 48 h and necrosis at 72 h leading to cell death were noted. Late apoptotic events and cell membrane cytoskeletal actin rearrangement observed were hypothesized to be induced by particle-mediated cellular ROS. This in addition to radical generation ability of TiO2 in the dark will help further in better understanding of the toxicity mechanism in cells beyond ROS generation. Copyright © 2016 John Wiley & Sons, Ltd.

JAK/STAT and TGF-ß activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans

“…Generation of ROS was also found for TiO 2 NPs without UV activation, using toxicity tests on various mammalian cells 23 . From a more mechanism perspective, non-photoactivated induction of ROS by TiO 2 NPs via dissolved oxygen was reported in a recent study 24 . This implies that one possible toxicity mechanism of TiO 2 NPs might arise from ROS, and UV photoactivation can worsen this oxidative stress by increasing the level of ROS.…”

Titanium dioxide nanoparticles induce COX-2 expression through ROS generation in human periodontal ligament cells

“…Since previous studies have reported that the treatment with various NPs, including titanium, resulted in the generation of ROS in multiple cell lines (Gali et al, 2016;Minai et al, 2013;Kundu et al, 2018) and the accumulation of intracellular ROS can induce COX-2 expression (Kundu et al, 2018;Nishanth et al, 2011), we examined whether TiO 2 -NPs accumulate intracellular ROS by measuring the fluorescence intensity of DCF-DA in PDL cells. The accumulation of ROS is induced by treatment of TiO 2 -NPs (2.5, 5 or 10 µg/mL) for 1 hr (Fig.…”

Improvement of mechanical-antibacterial performances of AR/PMMA with TiO2 and HPQM treated by N-2(aminoethyl)-3-aminopropyl trimethoxysilane

“…Work by Gali et al. 22 claimed that TiO 2 could generate O 2 − , HOO • , and HO − in the dark due to dissolved oxygen. Thus, it can be speculated that the oxygen from the environment and bacterial suspension could support the ROS generation from TiO 2 .…”

“…Regarding the effect of antibacterial property, the non-treated TiO 2 could generate the reactive oxygen species (ROS), producing O 2 − , HOO • , and HO − in the dark environment and HO • in the UV environment. 22 However, the effect of silane coupling agent on the mechanical and antibacterial properties of HPQM in the matrix is still not investigated.…”