- 作者：Williams ; R.E. ; Major ; H. ; Lock ; E.A. ; Lenz ; E.M. ; Wilson ; I.D.
- 关键词：d-AAO ; d-amino acid oxidase ; PCA ; principal component analysis ; d-Serine ; Proximal tubule ; Kidney ; HPLC&ndash ; MS ; Metabonomics
- 刊名：Toxicology
- 出版年：2005
- 期刊代码：47_0300483x
- 类别：pha
- 出版时间：February 14, 2005
- 卷：207
- 期：2
- 页码：179-190
- 文件大小：396 K
摘要
HPLC–MS-based metabonomic analysis was used to investigate urinary metabolic perturbations associated with d-serine-induced nephrotoxicity. d-Serine causes selective necrosis of the proximal straight tubules in the rat kidney accompanied by aminoaciduria, proteinuria and glucosuria. Alderely Park (Wistar-derived) rats were dosed with either d-serine (250mg/kg ip) or vehicle (deionised water) and urine was collected at 0–12, 12–24, 24–36 and 36–48h post-dosing. Samples were analysed using a Waters Alliance® HT 2795 HPLC system coupled to a Waters Micromass Q-ToF-micro™ equipped with an electrospray source operating in either positive or negative ion mode. Changes to the urinary profile were detected at all time points compared to control. In negative ion mode, increases were observed in serine (m/z