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

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