As titanium dioxide nanoparticles (TiO(2) NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO(2) NPs (dosed at 0.16, 0.4 and 1 g kg( - 1), respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by (1)H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO(2) NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, alpha-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO(2) NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO(2) NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO(2) NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

Although zinc oxide nanoparticles (ZnO NPs) have been widely used, their potential hazards on mammalian and human remain largely unknown. In this study, the biochemical compositions of urine and kidney from the rats treated with ZnO NPs (100, 300 and 1000 mg/kg, respectively) were investigated using (1)H nuclear magnetic resonance (NMR) technique with the pattern recognition of partial least squares-discriminant analysis. Hematology, clinical biochemistry and kidney histopathological examinations were also performed. Metabolic profiles from rats treated with ZnO NP(S) exhibited increases in the levels of taurine, lactate, acetate, creatine, phosphocholine, trimethylamine-N-oxide, α-glucose, and 3-D-hydroxybutyrate, as well as decreases in lipid, succinate, citrate, α-ketoglutarate, hippurate and 4-hydroxyphenylacetic acid in urine after ZnO NPs treatment for 14 days. A similar alteration pattern was also identified in kidney. Urine choline and phosphocholine increased significantly shortly after ZnO NPs treatment, moreover, some amino acids and glucose also increased during the experimental period. However, succinate, citrate and α-ketoglutarate in urine exhibited a different alteration trend, which showed increases on the first day after ZnO NPs treatment, but decreases gradually until the termination of the study. A similar alteration pattern of urinary (1)H NMR spectra was also detected in kidney. Moreover, ZnO NPs (1000 mg/kg) resulted in significant increases in serum creatine and blood urea nitrogen, decreases in hemoglobin, haematocrit and mean corpuscular hemoglobin concentration, and overt tubular epithelial cell necrosis. These findings show that ZnO NPs can disturb the energy metabolism and cause mitochondria and cell membrane impairment in rat kidney, which may contribute to ZnO NPs-induced nephrotoxicity.

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Cocaine dependence involves in the brain's reward circuit as well as nucleus accumbens (NAc), a key region of the mesolimbic dopamine pathway. Many studies have documented altered expression of genes and identified transcription factor networks and epigenetic processes that are fundamental to cocaine addiction. However, all these investigations have focused on mRNA of encoding genes, which may not always reflect the involvement of long non-coding RNAs (lncRNAs), which has been implied in a broad range of biological processes and complex diseases including brain development and neuropathological process. To explore the potential involvement of lncRNAs in drug addiction, which is viewed as a form of aberrant neuroplasticity, we used a custom-designed microarray to examine the expression profiles of mRNAs and lncRNAs in brain NAc of cocaine-conditioned mice and identified 764 mRNAs, and 603 lncRNAs were differentially expressed. Candidate lncRNAs were identified for further genomic context characterization as sense-overlap, antisense-overlap, intergenic, bidirection, and ultra-conserved region encoding lncRNAs. We found that 410 candidate lncRNAs which have been reported to act in cis or trans to their targeted loci, providing 48 pair mRNA-lncRNAs. These results suggest that the modification of mRNAs expression by cocaine may be associated with the actions of lncRNAs. Taken together, our results show that cocaine can cause the genome-wide alterations of lncRNAs expressed in NAc, and some of these modified RNA transcripts may to play a role in cocaine-induced neural plasticity and addiction.

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