NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticlesin rats after oral administration

Abstract

As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health hasattracted particular attention. In the present study, the oral toxicological effects ofTiO2 NPs (dosed at0.16, 0.4 and 1 g kg − 1, respectively) were investigated using conventional approaches and metabonomicanalysis in Wistar rats. Serum chemistry, hematology and histopathologyexaminations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partialleast squares discriminant analysis. The metabolic signature of urinalysis inTiO2 NP-treated rats showed increases in the levels of taurine, citrate,hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline,α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels oflactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), cholineand leucine were observed. The metabonomics analysis of serum showed increases inTMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases inglutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine afterTiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactatedehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed inTiO2 NP-treated rats. These findings indicate that disturbances in energyand amino acid metabolism and the gut microflora environment maybe attributable to the slight injury to the liver and heart caused byTiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive methodto study the biochemical effects of nanomaterials.