In vivo/in silico insight into the effect of titanium dioxide nanoparticle on serum paraoxonase 1 activity in rat

Serum paraoxonase1 (PON1) has special function in human body organism including the antioxidant and anti-atherogenic properties. In the present study, the effect of TiO2 nanoparticles on the activity and structure of the PON1 has been evaluated through in vivo and in silico methods. After treatments of the rats with different doses of TiO2 NPs, blood samples were collected and serum PON1 activity was measured by phenylacetate and paraoxon as substrate. In addition, the effects of TiO2 NP on enzyme structure were analyzed through Molecular dynamic (MD) simulation via Gromacs software package to obtain RMSD, RMSF, Rg, SASA, and secondary structures values. A significant reduction (p < 0.05) in arylesterase & paraoxonase activities of serum PON1 were monitored in Spectrometric assays when rats were treated with 150 and 200 mg/kg doses of TiO2 NPs. RMSD, RG, RMSF, and SASA values in the presence of TiO2 have been increased while RMSF values of the L1 and L2 loops (gate of the catalytic site) have been reduced. Moreover, Hydrogen bonds and secondary structure values of the enzyme decreased in the presence of TiO2 NP. All of these MD simulation results could indicate the instability of the PON1 structure bounded to TiO2 NP. TiO2 NP could cause a disturbance in the enzyme structure and function of PON1 based on the results. PON1 prevents oxidation of LDL and can delay atherosclerosis progression while in the presence of TiO2 NP these protective effects could be endangered.