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Investigations into the biochemical effects of region-specific nephrotoxins.
Abstract
1H NMR spectroscopy provides a useful initial biochemical screen with which to detect abnormal patterns of metabolites in urine collected from animals with different sites of nephrotoxic lesions. Male Fischer 344 rats were treated with nephrotoxic doses of sodium chromate (pars convoluta of proximal tubule), cisplatin, hexachlorobutadiene, mercury II chloride (pars recta of proximal tubule), propylene imine, and bromoethanamine (renal papilla) in order to induce damage in specific regions of the kidney. Urine was collected for up to 48 hr after dosing and was analyzed by 1H NMR spectroscopy (400 MHz) and conventional biochemical methods to provide biochemical fingerprints of urine in various site-specific nephrotoxic states. Hexachlorobutadiene and HgCl2 produced severe glycosuria and transient enzymuria. 1H NMR urinalysis revealed aminoaciduria, glycosuria, and lactic aciduria after exposure to all proximal tubular toxins except cisplatin, whereas papillary insult resulted in early elevations in urinary trimethylamine N-oxide and dimethylamine, together with later elevations in urinary acetate, succinate, and N,N-dimethylglycine (after propylene imine). Trimethylamine N-oxide and dimethylamine are suggested as novel markers of site-specific renal papillary injury in the rat.
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Cited by
Beckonert, O., Keun, H. C., Ebbels, T. M. D., Bundy, J., Holmes, E., Lindon, J. C., & Nicholson, J. K. (2007) · Nature Protocols · doi:10.1038/nprot.2007.376 · Cited by 2,109
Self-citationDona, A. C., Jiménez, B., Schäfer, H., Humpfer, E., Spraul, M., Lewis, M. R., Pearce, J. T. M., Holmes, E., Lindon, J. C., & Nicholson, J. K. (2014) · Analytical Chemistry · doi:10.1021/ac5025039 · Cited by 540
Self-citationNMR‐based metabonomic approaches for evaluating physiological influences on biofluid composition
Bollard, M. E., Stanley, E. G., Lindon, J. C., Nicholson, J. K., & Holmes, E. (2005) · NMR in Biomedicine · doi:10.1002/nbm.935 · Cited by 473
Self-citationLindon, J. C., Holmes, E., Bollard, M. E., Stanley, E. G., & Nicholson, J. K. (2004) · Biomarkers · doi:10.1080/13547500410001668379 · Cited by 451
Self-citationLindon, J. C., Nicholson, J. K., & Everett, J. R. (1999) · Annual Reports on NMR Spectroscopy · doi:10.1016/s0066-4103(08)60035-6 · Cited by 395
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Metadata
- Authors
- Gartland, K. P., Bonner, F. W., & Nicholson, J. K.
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 1989-02
- Volume
- 35
- Issue
- 2
- Pages
- 242-250
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2344279945
- Cited by
- 213
- References
- 0
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- closed
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- Gartland, K. P., Bonner, F. W., & Nicholson, J. K. (1989). Investigations into the biochemical effects of region-specific nephrotoxins. Molecular Pharmacology. https://doi.org/10.1016/s0026-895x(25)10952-8
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