Acrylamide coadministration modulates hepatic ROS-mediated apoptotic DNA damage and inflammation induced by TiO2 nanoparticles in mice

Abstract

The widespread human consumption of food and commercial products containing acrylamide and titanium dioxide (TiO2) nanoparticles highlights the need to assess the risks of their concurrent exposure. However, almost no studies have explored the effect of acrylamide and TiO2 nanoparticles co-exposure on genomic DNA integrity and inflammation induction in hepatic tissues. Consequently, this study aimed to estimate the impact of acrylamide and TiO2 nanoparticles coadministration on the genomic DNA integrity, reactive oxygen species (ROS) generation and expression level of apoptotic and inflammatory genes in mice hepatic tissues. Mice were orally administered acrylamide (3 mg/kg) or/and TiO2 nanoparticles (5 mg/kg) five times a week over two successive weeks. Genomic DNA integrity was assessed using alkaline Comet and Laddered DNA fragmentation assays, while ROS level was measured using 2, 7- Dichlorofluorescein diacetate dye. The expression level of inflammatory and apoptotic genes was quantified using quantitative real-time PCR (qRT-PCR). The results indicated that either acrylamide (3 mg/kg) or TiO2 nanoparticles (5 mg/kg) alone significantly disrupted DNA integrity, increased ROS level, and upregulated inflammatory (INOS, COX-2) and apoptotic (p53) gene expression, while downregulating the anti-inflammatory HO-1 gene. However, the coadministration of acrylamide and TiO2 nanoparticles resulted in even greater DNA damage, higher ROS production, and a further increase in inflammatory and apoptotic gene expression, along with a more pronounced decrease in HO-1 expression compared to the effects of either agent alone. In conclusion these findings suggest that chronic coadministration of acrylamide and TiO2 nanoparticles, even at low doses, amplifies the genomic DNA damage and inflammation induced by each agent individually, exacerbating hepatic cell stress. Therefore, avoiding simultaneous exposure to acrylamide and TiO2 nanoparticles is recommended to reduce the risk of severe toxic effects.