Studies of single-walled carbon nanotubes-induced hepatotoxicity by NMR-based metabonomics of rat blood plasma and liver extracts

The toxicological effects of single-walled carbon nanotubes (SWCNTs) were investigated after intratracheal instillation in male Wistar rats over a 15-day period using metabonomic analysis of 1H (nuclear magnetic resonance) NMR spectra of blood plasma and liver tissue extracts. Concurrent liver histopathology examinations and plasma clinical chemistry analyses were also performed. Significant changes were observed in clinical chemistry features, including alkaline phosphatase, total protein, and total cholesterol, and in liver pathology, suggesting that SWCNTs clearly have hepatotoxicity in the rat. 1H NMR spectra and pattern recognition analyses from nanomaterial-treated rats showed remarkable differences in the excretion of lactate, trimethylamine oxide, bilineurin, phosphocholine, amylaceum, and glycogen. Indications of amino acid metabolism impairment were supported by increased lactate concentrations and decreased alanine concentrations in plasma. The rise in plasma and liver tissue extract concentrations of choline and phosphocholine, together with decreased lipids and lipoproteins, after SWCNTs treatment indicated a disruption of membrane fluidity caused by lipid peroxidation. Energy, amino acid, and fat metabolism appeared to be affected by SWCNTs exposure. Clinical chemistry and metabonomic approaches clearly indicated liver injury, which might have been associated with an indirect mechanism involving nanomaterial-induced oxidative stress.

[1]  Sangdun Choi,et al.  Biological Toxicity and Inflammatory Response of Semi-Single-Walled Carbon Nanotubes , 2011, PloS one.

[2]  Xian-Zhong Yan,et al.  Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR-spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts. , 2006, Toxicology and applied pharmacology.

[3]  Leo L. Cheng,et al.  NMR-based metabolomics approach to target biomarkers for human prostate cancer , 2007, Expert review of proteomics.

[4]  Jing Zhao,et al.  NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure to PCBs and TCDD in rats. , 2010, Toxicology and applied pharmacology.

[5]  E Holmes,et al.  Chemometric analysis of biofluids following toxicant induced hepatotoxicity: A metabonomic approach to distinguish the effects of 1-naphthylisothiocyanate from its products , 2005, Xenobiotica; the fate of foreign compounds in biological systems.

[6]  Brian C Sweatman,et al.  Effects of feeding and body weight loss on the 1H-NMR-based urine metabolic profiles of male Wistar Han Rats: Implications for biomarker discovery , 2004, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[7]  Jing-yu Wei,et al.  Changes of metabolic profiles in urine after oral administration of quercetin in rats. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[8]  J. Nagy,et al.  Respiratory toxicity of multi-wall carbon nanotubes. , 2005, Toxicology and applied pharmacology.

[9]  Elaine Holmes,et al.  Metabonomic deconvolution of embedded toxicity: application to thioacetamide hepato- and nephrotoxicity. , 2005, Chemical research in toxicology.

[10]  E Holmes,et al.  Chemometric models for toxicity classification based on NMR spectra of biofluids. , 2000, Chemical research in toxicology.

[11]  Huifeng Wu,et al.  Metabolic profiling studies on the toxicological effects of realgar in rats by (1)H NMR spectroscopy. , 2009, Toxicology and applied pharmacology.

[12]  D. Baunsgaard,et al.  Combination of ‘omics’ data to investigate the mechanism(s) of hydrazine-induced hepatotoxicity in Rats and to identify potential biomarkers , 2004, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[13]  Qingxiu Wang,et al.  Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: a rapid in vivo screening method for nanotoxicity. , 2008, Toxicology and applied pharmacology.

[14]  M. Ema,et al.  Genotoxicity evaluation for single‐walled carbon nanotubes in a battery of in vitro and in vivo assays , 2013, Journal of applied toxicology : JAT.

[15]  V. Castranova,et al.  Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes. , 2009, Toxicology.

[16]  Stefano Tiziani,et al.  Early stage diagnosis of oral cancer using 1H NMR-based metabolomics. , 2009, Neoplasia.

[17]  Chen Wang,et al.  Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[18]  V. Castranova,et al.  Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus? , 2009, Pharmacology & therapeutics.

[19]  J. Lindon,et al.  NMR‐based metabonomic approaches for evaluating physiological influences on biofluid composition , 2005, NMR in biomedicine.

[20]  P. Tchounwou,et al.  Biochemical and histopathological evaluation of functionalized single‐walled carbon nanotubes in Swiss–Webster mice , 2011, Journal of applied toxicology : JAT.

[21]  U. Günther,et al.  Early Stage Diagnosis of Oral Cancer Using 1 H NMR – Based Metabolomics 1,2 , 2009 .

[22]  Y. Rosen,et al.  Carbon nanotubes in drug delivery: focus on infectious diseases. , 2009, Expert opinion on drug delivery.

[23]  Á. Jos,et al.  Influence of carboxylic acid functionalization on the cytotoxic effects induced by single wall carbon nanotubes on human endothelial cells (HUVEC). , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[24]  John C Lindon,et al.  Integrated application of transcriptomics and metabonomics yields new insight into the toxicity due to paracetamol in the mouse. , 2004, Journal of pharmaceutical and biomedical analysis.