Estimation of genotoxicity, apoptosis and oxidative stress induction by TiO2 nanoparticles and acrylamide subacute oral coadministration in mice

Abstract

Acrylamide is used in the industry and can be a by-product of high-temperature food processing which has toxic potential in various tissues, and titanium dioxide nanoparticles (TiO₂NPs) are widely used in toothpaste, sweets, food perseveration, chewing gum and medicines. Consequently, humans are daily exposed to large amounts of acrylamide and TiO₂NPs mainly through food intake. However, limited studies are available on the effect of simultaneously intake of acrylamide and TiO₂NPs on the integrity of genomic DNA and the induction of apoptosis in brain tissues. Therefore, this study estimated the influence of acrylamide coadministration on TiO₂NPs induced genomic instability and oxidative stress in the brain tissues of mice. To achieve this, mice were orally administrated acrylamide (3 mg/kg b.w) or/and TiO₂NPs (5 mg/kg b.w) for two successive weeks (5 days per week). The comet assay results showed that concurrent oral administration of acrylamide and TiO₂NPs strongly induced single- and double stranded DNA breaks, and that the level of reactive oxygen species (ROS) was also highly elevated within neural cells after simultaneous oral intake of acrylamide and TiO₂NPs compared to those observed after administration of acrylamide or/TiO₂NPs alone. Moreover, oral co-administration of acrylamide with TiO₂NPs increased apoptotic DNA damage to neurons by upregulating the expression levels of P53, TNF-α, IL-6 and Presenillin-1 genes compared to groups administered TiO₂NPs. Therefore, from these results, the present study concluded that coadministration of acrylamide renders TiO₂NPs more genotoxic and motivates apoptotic DNA damage and oxidative stress induced by TiO₂NPs in brain cells, and thus it is recommended to avoid concurrent oral acrylamide administration with TiO₂NPs.