Estimation of genomic and mitochondrial DNA integrity in the renal tissue of mice administered with acrylamide and titanium dioxide nanoparticles

评估施用丙烯酰胺和二氧化钛纳米颗粒的小鼠肾脏组织中基因组和线粒体DNA的完整性

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Abstract

The Kidneys remove toxins from the blood and move waste products into the urine. However, the accumulation of toxins and fluids in the body leads to kidney failure. For example, the overuse of acrylamide and titanium dioxide nanoparticles (TiO(2)NPs) in many food and consumer products increases human exposure and risks; however, there are almost no studies available on the effect of TiO(2)NPs coadministration with acrylamide on the integrity of genomic and mitochondrial DNA. Accordingly, this study was conducted to estimate the integrity of genomic and mitochondrial DNA in the renal tissue of mice given acrylamide and TiO(2)NPs. To achieve this goal, mice were administrated orally TiO(2)NPs or/and acrylamide at the exposure dose levels (5 mg/kg b.w) and (3 mg/kg b.w), respectively, five times per week for two consecutive weeks. Concurrent oral administration of TiO(2)NPs with acrylamide caused remarkable elevations in the tail length, %DNA in tail and tail moment with higher fragmentation incidence of genomic DNA compared to those detected in the renal tissue of mice given TiO(2)NPs alone. Simultaneous coadministration of TiO(2)NPs with acrylamide also caused markedly high elevations in the reactive oxygen species (ROS) production and p53 expression level along with a loss of mitochondrial membrane potential and high decreases in the number of mitochondrial DNA copies and expression level of β catenin gene. Therefore, from these findings, we concluded that concurrent coadministration of acrylamide with TiO(2)NPs augmented TiO(2)NPs induced genomic DNA damage and mitochondrial dysfunction through increasing intracellular ROS generation, decreasing mitochondrial DNA Copy, loss of mitochondrial membrane potential and altered p53 and β catenin genes expression. Therefore, further studies are recommended to understand the biological and toxic effects resulting from TiO(2)NPs with acrylamide coadministration.

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