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Issue 6, 2004
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A metabonomic investigation of the biochemical effects of mercuric chloride in the rat using 1H NMR and HPLC-TOF/MS: time dependant changes in the urinary profile of endogenous metabolites as a result of nephrotoxicity

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Abstract

The effects of the administration of a single dose of the model nephrotoxin mercuric chloride (2.0 mg kg−1, subcutaneous) to male Wistar-derived rats on the urinary metabolite profiles of a range of endogenous metabolites has been investigated using 1H NMR and HPLC-MS. Urine samples were collected daily for 9 days from both dosed and control animals. Analysis of these samples revealed marked changes in the pattern of endogenous metabolites as a result of HgCl2 toxicity. Peak disturbances in the urinary metabolite profiles were observed (using both NMR and HPLC-MS) at 3 days post dose. Thereafter the urinary metabolite profile gradually returned to a more normal composition. Markers of toxicity identified by 1H NMR spectroscopy were raised concentrations of lactate, alanine, acetate, succinate, trimethylamine (TMA), and glucose. Reductions in the urinary excretion of citrate and α-ketoglutarate were also seen. Markers identified by HPLC-MS, in positive ion mode, were kynurenic acid, xanthurenic acid, pantothenic acid and 7-methylguanine which decreased after dosing. In addition an ion at m/z 188, probably 3-amino-2-naphthoic acid, was observed to increase after dosing. As well as these identified compounds other ions at m/z 297 and 267 decreased after dosing. In negative ion mode a range of sulfated compounds were observed, including phenol sulfate and benzene diol sulfate, which decreased after dosing. As well as the sulfated components an unidentified glucuronide at m/z 326 was also observed to decrease after dosing. The results of this study demonstrate the complementary nature of the NMR and MS-based techniques for metabonomic analysis.

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Publication details

The article was received on 06 Jan 2004, accepted on 29 Mar 2004 and first published on 21 Apr 2004


Article type: Paper
DOI: 10.1039/B400159C
Citation: Analyst, 2004,129, 535-541
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    A metabonomic investigation of the biochemical effects of mercuric chloride in the rat using 1H NMR and HPLC-TOF/MS: time dependant changes in the urinary profile of endogenous metabolites as a result of nephrotoxicity

    E. M. Lenz, J. Bright, R. Knight, I. D. Wilson and H. Major, Analyst, 2004, 129, 535
    DOI: 10.1039/B400159C

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