Metabonomics with 1H-NMR spectroscopy and liquid chromatography-mass spectrometry applied to the investigation of metabolic changes caused by gentamicin-induced nephrotoxicity in the rat

摘要: AbstractThe model nephrotoxin gentamicin was administered to male Wistar-derived rats daily, for 7 days, at 60 mg kg−1 day−1, subcutaneously, twice daily. Conventional clinical chemistry urinalysis showed a significant increase in N-acetyl-β-D-glucosaminidase (NAG) activity from day 3. At necropsy on 9, clear histological damage the kidney noted with all animals showing generally severe nephropathy primarily focused proximal convoluted tubules. The urinary excretion pattern of endogenous metabolites over time course study studied using combination 1H-NMR spectroscopy and HPLC-TOF-MS/MS electrospray ionization (ESI). Changes as result daily administration were readily detected by both techniques perturbations profile observed onwards. findings included raised glucose reduced trimethylamine N-oxide (TMAO). metabonomic profiles ...