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compared to control. PF-6463922 ic50 Discussion Recent studies have shown that metabonomic approach can be used as a rapid analytical tool for the study on effects of hepatotoxic compounds [22–24]. In this study, NMR-based metabonomic methods coupled with traditional clinical chemistry and histopathology methods were used to demonstrate SWCNTs exposure-induced hepatotoxicity in rats. The complex disturbances in the endogenous metabolite profiles of rat biofluids combined with remarkable histopathological evidence and the change of the BAY 11-7082 supplier plasma enzyme concentrations could be related to nanoparticle-induced hepatotoxicity. SWCNTs were found here to show effects on the chemistry and histopathology of rat blood and liver. Obviously, changes were observed in clinical chemistry features, including AZD8931 mouse ALP, TP, and TC, and in liver pathology (Table 1 and Figure 2, respectively), suggesting that SWCNTs clearly have

hepatotoxic abilities in rats. The release of cellular hepatospecific enzymes, such as ALP, might have resulted from nanoparticle-induced damage of cell membrane integrity, and the observed reduced TP suggested perturbation of protein biosynthesis and catabolism. From these observations, SWCNTs appeared to produce hepatotoxicity via discrete pathophysiologic necrosis and inflammation. The obtained PCA data were in good agreement with the histopathology and clinical chemistry data, with the metabonomic analytical results being more sensitive than clinical chemistry analyses. The PCA of 1H NMR data showed that, in rat plasma and liver tissue, SWCNTs exposure altered the concentrations of glutamate, creatine, lactate, TMAO, cho, HDL, VLDL, and glucose and that these altered metabolites might be considered possible biomarkers for such hepatotoxicity. SWCNTs exposure appeared to induce energy metabolism disturbances, with choline and phosphocholine being breakdown products of phosphatidylcholine, the major membrane constituent. After SWCNTs treatment, the observed rise in plasma choline and phosphocholine concentrations,

Cepharanthine together with a drop in plasma lipids and lipoproteins, denoted a disruption of membrane fluidity caused by lipid peroxidation [25]. The increased glutamine concentration in aqueous soluble extracts of liver tissues resulted from the cytosolic accumulation of glutamine, which was due to defective GSH transport from the cytosol into the mitochondria, as a result of decreased membrane fluidity due to the decreased content of unsaturated fatty acids in cellular membranes [14, 26]. The glucose concentrations in plasma spectra and those of glucose and glycogen in aqueous soluble liver extract were decreased significantly in rats after SWCNTs treatment, which suggested that the rates of glycogenolysis and glycolysis increased because of inhibited lipid metabolism in these animals.