期刊
BIOCHEMICAL PHARMACOLOGY
卷 64, 期 1, 页码 67-77出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(02)01016-X
关键词
alpha-naphthylisothiocyanate; magic angle spinning; MAS H-1 NMR spectroscopy; liver; Han-Wistar rat; metabonomics; aqueous extract; chlorofonn/methanol extract
The metabolite profiles from livers of toxin-treated rats were investigated using high resolution H-1 NMR spectroscopy of aqueous (acetonitrile/water), lipidic (chloroform/methanol) extracts and magic angle spinning (MAS)-NMR spectroscopy of intact tissue. Rats were treated with the model cholestatic hepatotoxin, alpha-naphthylisothiocyanate (ANIT, 150 mg/kg) and NMR spectra of liver were analysed using principal components analysis (PCA) to extract novel toxicity biomarker information. H-1 NMR spectra of control aqueous extracts showed signals from a range of organic acids and bases, amino acids, sugars, and glycogen. Chloroform/methanol extracts showed signals from a range of saturated and unsaturated triglycerides, phospholipids and cholesterol. The MAS H-1 NMR spectra of livers showed a composite of signals found in both aqueous and lipophilic extracts. Following ANIT treatment, H-1 NMR-PCA of aqueous extracts indicated a progressive reduction in glucose and glycogen, together with increases in bile acid, choline, and phosphocholine signals. H-1 NMR-PCA of chloroform/methanol extracts showed elevated triglyceride levels. The H-1 MAS-NMR-PCA analysis allowed direct detection of all of the ANIT-induced tissue perturbations revealed by H-1 NMR of extracts, enabling metabolic characterisation of the lesion, which included steatosis, bile duct obstruction and altered glucose/glycogen metabolism. MAS-NMR spectroscopy requires minimal sample preparation and, unlike H-1 NMR spectroscopy of tissue extracts, does not discriminate metabolites based on their solubility in a particular solvent and so this is a particularly useful exploratory tool in biochemical toxicology. (C) 2002 Elsevier Science Inc. All rights reserved.
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