There is a noticeable increase in the use of nanomaterials and its compounds, which requires further research in their cytotoxicity and toxic effects. The most important of these materials is titanium dioxide nanoparticles TiO2 due to its effectiveness and utilization in a huge range of applications. The study showed that TiO2 NP had an impact on the organs coefficient of treated groups, there was change in the concentration of cellular mediators in the homogenate tissue and in BALF throughout the study period. Many histopathological changes in the lung and liver of all treated groups were observed comparing with the control group; this increased as the concentration increased and according to the exposure period. The study showed that the TiO2 NP has effect on gene expression of MMP-12 using immunohistochemistry technique, there was a decrease in MMP-12 expression in all treatment groups after four days of intratracheal instillation, while after month and three months of intratracheal instillation, there was a significant increased comparing with four days. The analysis of RT-qPCR showed down regulate significantly in the gene expression of (MMP-1, MMP-2, MMP12, Collagen I).
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