Systemic effect of TiO₂ micro‐ and nanoparticles after acute exposure in a murine model

Abstract

The surface of a biomedical implant can be a potential endogenous source of release of microparticles (MPs) and nanoparticles (NPs) into the biological environment. In addition, titanium particles from exogenous sources can enter the body through inhalation, ingestion, or dermal contact. The aim of this work was to evaluate the biological response of the lung, liver, and kidneys to acute exposure to titanium dioxide (TiO 2 ). Male Wistar rats were intraperitoneally injected with a suspension of 45 μm or 5 nm TiO 2 particles. One month post-exposure, titanium concentration was determined spectrometrically (ICP-MS) in plasma and target organs. Blood smears and organ tissue samples were examined histopathologically, and oxidative metabolism was analyzed (superoxide anion by nitro blue tetrazolium (NBT) test; superoxide dismutase (SOD) and catalase (CAT); lipid peroxidation; paraoxonase 1). Liver (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and kidney (urea, creatinine) function was evaluated using serum biochemical markers. Microchemical and histological analysis revealed the presence of particles, though no structural alterations, in TiO 2 -exposed groups. NBT test showed an increase in the percentage of reactive cells and antioxidant enzyme consumption in lung samples in the 45 μm and 5 nm TiO 2 -exposed groups. Only the 5 nm particles caused a decrease in SOD and CAT activity in the liver. No changes in renal oxidative metabolism were observed in either of the TiO 2 -exposed groups. Determination of serum biochemical markers and analysis of oxidative metabolism are not early bioindicators of tissue damage caused by TiO 2 MPs and NPs.

Chronic exposure to TiO2 micro‐ and nano particles: A biochemical and histopathological experimental study

“…The observed increase is likely due to the translocation of particles from target and other organs, like the spleen and lymph nodes, to the bloodstream. Plasma levels of titanium (Ti) in the TiO 2 ‐NP5 and TiO 2 ‐MP45 groups 6 months postexposure were 47% and 34% lower, respectively, compared with the levels we observed 1 month postexposure in our previous study 41 …”

“…39 Tissue response to these particles is determined not only by the physical-chemical properties of the particles, such as average particle size (APS), shape, concentration, and chemical structure but also by host-related factors like age, sex, and genetic profile. 40,41 In line with reports in the literature, we detected titaniumbased particles in peri-implant tissue surrounding failed human dental implants, 42 oral mucosa covering titanium-based implant cover screws, 43 cells exfoliated from oral mucosa in contact with titaniumbased dental implants, 44 reactive lesions in peri-implant oral mucosa, 45 and infrequent titanium-based dental implant-related pathologies. 38 Previous experimental animal research conducted by our group provides histological evidence of the presence of particles in the peri-implant bed of titanium-based implants 12 and in exfoliated cheek mucosa cells after systemic titanium contamination.…”

“…In keeping with the present results, we observed no structural damage in the tissues in our previous study (after acute exposure). 41 Antioxidant species are capable of preventing the damage caused by oxidant species generated by TiO 2 NPs/MPs in the lung early after their generation.…”

“…Plasma levels of titanium (Ti) in the TiO 2 -NP5 and TiO 2 -MP45 groups 6 months postexposure were 47% and 34% lower, respectively, compared with the levels we observed 1 month postexposure in our previous study. 41 Biological systems maintain a delicate balance between oxidants and antioxidants. Oxidants must be detoxified to avoid damage to the tissues, and it is the antioxidant defense system that prevents injury via reduction and/or dismutation of O 2 À and its protonated forms.…”

“…47 A recent study conducted by our research team evaluating the effect of acute exposure (1 month) to TiO 2 MPs, and NPs on serum and target organs showed that neither serum biochemical markers nor oxidative metabolism indicators served as early biomarkers of tissue damage in response to TiO 2 . 41 Our hypothesis was that TiO Blood samples (3 mL) were collected by tail vein puncture prior to euthanasia. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL), 53,54 and the lungs, liver, and kidneys were resected immediately after euthanasia.…”