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.