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

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 (TiO₂NPs) in many food and consumer products increases human exposure and risks; however, there are almost no studies available on the effect of TiO₂NPs 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 TiO₂NPs. To achieve this goal, mice were administrated orally TiO₂NPs 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 TiO₂NPs 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 TiO₂NPs alone. Simultaneous coadministration of TiO₂NPs 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 TiO₂NPs augmented TiO₂NPs 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 TiO₂NPs with acrylamide coadministration.

Figure 1

Representative photo for the seen electrophoresed pattern of renal genomic DNA extracted from negative control mice (C) and mice given orally acrylamide (A) and TiO₂NPs (T) separately or simultaneously together (AT). M: Marker. Three samples were analyzed per each group.

Figure 2

Representative photos for the scored Comet nuclei in the renal cells of the negative control mice and mice given orally acrylamide and TiO₂NPs separately or simultaneously together.

Figure 3

Representative photos for the mitochondrial membrane permeability potential observed in the renal cells of the negative control mice and mice given orally acrylamide and TiO₂NPs separately or simultaneously together.

Figure 4

Variation in the copy of mitochondrial DNA in the renal cells of the negative control mice and mice given orally acrylamide and TiO₂NPs separately or simultaneously together. Six mice were analyzed for each group. Results are expressed as mean ± SD and analyzed using one-way analysis of variance followed by Duncan’s test to test the similarity between the control and three treated groups. Means with different letters indicates statistical significant difference between the compared groups at a significant level p < 0.001.

Figure 5

Representative photos for the ROS level generated within the renal cells of the negative control mice and mice given orally acrylamide and TiO₂NPs separately or simultaneously together.