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.