Pathophysiological Effects of Titanium Dioxide Nanoparticles and the Protective Role of Piperine and a Piperine-TiO₂NP Combination in Rats.

<ns3:p> Background This study aimed to evaluate the protective role of piperine and piperine-loaded titanium dioxide nanoparticles on oxidative and biochemical parameters, antioxidant levels, and cytogenetic parameters in the brain. Methods forty rats were randomly divided into four equal groups for 35 days as follow: the control group was administered DW/IP; the G1 group received 40 mg/kg B.W. of piperine orally; The G2 group was given TiO2NPs (50 mg/kg B.W.)/i.p. received; and the G3 group received 75 mg/kg B.W. /I. P. of PIP-TiO2NPs. Results A significant increase in serum TAO-C and a significant decrease in ROS were observed in G1 and G3 compared to G2 and the control groups. A significant reduction in serum neurotransmitter concentration was found in the G2 group compared to the G1, control, and G3 groups, while a significant increase was observed in the G1 group. Gene expression data for cyclooxygenase showed upregulation in the G2 group and was significantly higher than in the G3, G1, and control groups. Histopathological examination showed normal brain layers, hippocampus, and thalamus appearance in G1, G2, G3, and the control groups. The G2 group showed mild vascular congestion, hyperplasia, and mild disruption in the molecular cell layer of the cerebral cortex. The hippocampus of the G3 group showed moderate vacuolation with glial reduction. Conclusions These findings indicate that piperine, combined with TiO <ns3:sub>2</ns3:sub> NPs (PIP-TiO <ns3:sub>2</ns3:sub> NPs), provides neuroprotection by reducing oxidative stress and inflammatory responses induced by TiO <ns3:sub>2</ns3:sub> NPs in the rat brain. </ns3:p>