Metabonomic Studies of Biochemical Changes in the Serum of Rats by Intratracheally Instilled TiO₂ Nanoparticles

In vivo behavior of nanoparticles and interactions between nanoparticles and organisms are key components of nanotoxicology. In this study, the biochemical compositions of rat serum exposed to TiO₂ nanoparticles (nano-TiO₂) by intratracheal instillation at low (0.8 mg/kg), medium (4 mg/kg) and high doses (20 mg/kg) were investigated using ¹H-NMR techniques with pattern recognition methods. Serum biochemical assays, as well as histopathological and transmission electron microscopy (TEM) examinations of tissues were performed. ¹H-NMR spectra and pattern recognition analyses of nano-TiO₂ treated animals showed increased serum levels of ketone bodies, choline, low density lipoprotein (LDL), alanine and GLU, and decreased levels of lactate, creatine and pyruvate. Clinical chemistry analyses of serum showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. Furthermore, TEM provided an analysis of particle-related structural changes of the lungs, liver and kidneys, and revealed that the localization of nanoparticles within cells induced apoptosis. The damage to the target organs was associated with the perturbation of energy metabolism. Serum ¹H-NMR spectra, in combination with pattern recognition techniques, proved to be an efficient and simple metabonomic method to depict the metabolic changes produced by intratracheally-instilled nano-TiO₂.