Investigation of metabolite alteration in dimethylnitrosamine-induced liver fibrosis by GC-MS.

BACKGROUND A metabolomic study of biomarkers associated with dimethylnitrosamine (DMN)-induced hepatic fibrosis in Sprague-Dawley rats was performed using GC-MS. The clinical chemistry of the collected blood and the histopathology of excised liver samples were examined, and urine samples were prepared by solvent extraction. RESULTS Through pattern analysis, the DMN-treated group was divided into two subgroups based on the aspartate aminotransferase (AST) levels compared with the control, a moderately higher group (DMN subgroup A) and a significantly higher group (DMN subgroup B). Uric acid, orotic acid, N-phenylacetylglycine and glutaric acid were biomarkers for DMN subgroup A, aminomalonic acid was a biomarker for DMN subgroup B, and arabitol level distinguished control versus DMN treatment regardless of AST level. CONCLUSION This study suggests that the identification and profiling of AST level-related metabolites may be useful as a diagnostic tool and for the study of the mechanism of liver fibrosis induced by DMN.

[1]  H. Son,et al.  Protective Effect of Korean Red Ginseng against Aflatoxin B1-Induced Hepatotoxicity in Rat , 2011, Journal of ginseng research.

[2]  Aziza A. El‐Nekeety,et al.  Therapeutic Effects of Korean Red Ginseng Extract in Egyptian Patients with Chronic Liver Diseases , 2011 .

[3]  W. Carey,et al.  Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete? , 2010, Cleveland Clinic Journal of Medicine.

[4]  S. Kwon,et al.  Protective Effect of Morin on Dimethylnitrosamine-Induced Hepatic Fibrosis in Rats , 2009, Digestive Diseases and Sciences.

[5]  M. Donaghy.  INTERFACE OF NEUROLOGY AND INTERNAL MEDICINE , 2008, Neurology.

[6]  Tao-Tao Liu,et al.  A serum metabolomic investigation on hepatocellular carcinoma patients by chemical derivatization followed by gas chromatography/mass spectrometry. , 2008, Rapid communications in mass spectrometry : RCM.

[7]  W. Cho,et al.  Metabolomics and biomarker discovery: NMR spectral data of urine and hepatotoxicity by carbon tetrachloride, acetaminophen, and d-galactosamine in rats , 2008, Metabolomics.

[8]  Yuan Chen,et al.  Iron deposition and fat accumulation in dimethylnitrosamine-induced liver fibrosis in rat. , 2007, World journal of gastroenterology.

[9]  Liping Zhao,et al.  Pharmacometabonomic phenotyping reveals different responses to xenobiotic intervention in rats. , 2007, Journal of proteome research.

[10]  J. Lindon,et al.  Pharmaco-metabonomic phenotyping and personalized drug treatment , 2006, Nature.

[11]  P. Roderick,et al.  Performance of serum marker panels for liver fibrosis in chronic hepatitis C. , 2006, Journal of hepatology.

[12]  G. Hortobagyi,et al.  Pharmacogenomics and clinical biomarkers in drug discovery and development. , 2005, American journal of clinical pathology.

[13]  R. Njålsson.  Glutathione synthetase deficiency , 2005, Cellular and Molecular Life Sciences CMLS.

[14]  J. Lindon,et al.  Metabonomics and its role in drug development and disease diagnosis , 2004, Expert review of molecular diagnostics.

[15]  C. Waterfield,et al.  Phenylacetylglycine, a putative biomarker of phospholipidosis: Its origins and relevance to phospholipid accumulation using amiodarone treated rats as a model , 2004, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[16]  M. Knaap,et al.  Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway. , 2001, American journal of human genetics.

[17]  J. George,et al.  Biochemical abnormalities during the progression of hepatic fibrosis induced by dimethylnitrosamine. , 2000, Clinical biochemistry.

[18]  P. Hollenberg,et al.  Alkylation of cellular macromolecules and target specificity of carcinogenic nitrosodialkylamines: metabolic activation by cytochromes P450 2B1 and 2E1. , 1997, Carcinogenesis.

[19]  S. Copley,et al.  Detection and possible origins of aminomalonic acid in protein hydrolysates. , 1992, Analytical biochemistry.

[20]  J. Milner,et al.  Species comparison of the influence of ammonia on orotic acid and urea biosynthesis in liver. , 1984, The Journal of nutrition.

[21]  Jerry R. Mitchell,et al.  Metabolic Activation of Drugs to Toxic Substances , 1975 .

[22]  E. Reynolds.  Comparison of early injury to liver endoplasmic reticulum by halomethanes, hexachloroethane, benzene, toluene, bromobenzene, ethionine, thioacetamide and dimethylnitrosamine. , 1972, Biochemical pharmacology.

[23]  B. Marks.  THE BIOCHEMISTRY OF FOREIGN COMPOUNDS , 1969 .

[24]  P. Magee,et al.  Some Toxic Properties of Dimethylnitrosamine , 1954, British journal of industrial medicine.

[25]  Chi-Ying F. Huang,et al.  Global gene expression profiling of dimethylnitrosamine-induced liver fibrosis: from pathological and biochemical data to microarray analysis. , 2006, Gene expression.

[26]  Archer Mc.  Mechanisms of action of N-nitroso compounds. , 1989, Cancer surveys.

[27]  H. Zimmerman.  Hepatotoxicity: The adverse effects of drugs and other chemicals on the liver , 1978 .

[28]  J. Mitchell,et al.  Progress in hepatology. Metabolic activation of drugs to toxic substances. , 1975, Gastroenterology.

[29]  F. Renger.  [Progress in hepatology]. , 1968, Deutsche Zeitschrift fur Verdauungs- und Stoffwechselkrankheiten.

[30]  P. Magee,et al.  Carcinogenic nitroso compounds. , 1967, Advances in cancer research.

[31]  C. Rouiller.  CHAPTER 22 – EXPERIMENTAL TOXIC INJURY OF THE LIVER1 , 1964 .

[32]  J. Knight,et al.  Ciba Foundation Symposium - Cellular Injury , 1964 .