H-1 NMR spectroscopic and histopathological studies on propyleneimine-induced renal papillary necrosis in the rat and the multimammate desert mouse (Mastomys natalensis)

The renal papillary toxin, propyleneimine (PI), was administered at 20 or 30 mu l/kg i.p. to male Sprague Dawley (SD) rats (n = 5), Fischer 344 (F344) rats (n = 4), and to multimammate desert mice (Mastomys natalensis, n = 4). Urine was collected at time points up to 4 days p.d. and the toxicological response of the different animal models to PI compared using H-1 NMR spectroscopy of urine, renal histopathology, and urinary assays for alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (gamma GT). The renal papillae of both F344 and SD rats showed extensive necrotic lesions 4 days post-dosing and in some cases sloughing of the papilla. However, only slight renal papillary necrosis (RPN) was observed in Mastomys treated with 20 mu l/kg PI and, although slight to moderate damage was observed at 30 mu l/kg, PI-treated Mastomys showed substantially less RPN than either group of PI-treated rats. H-1 NMR urinalysis showed that PI treatment caused a decrease in the urinary concentrations of succinate (0-24 hr p.d.) and citrate (24-48 hr p.d.) and an increase in creatine (0-48 hr p.d.) in all animal models. Trimethylamine-N-oxide (24-48 hr) and 2-oxoglutarate concentrations decreased initially following the administration of PI and then rose above control levels. The H-1 NMR-detected urinary biochemical effects of PI in all three models were similar. However, taurine concentrations were elevated in the urine of Mastromys following PI treatment, perhaps indicating a degree of liver damage, whereas taurinuria was not seen in either SD or F344 rats. These observations are discussed in relation to the potential mechanism of PI-toxicity. (C) 1997 Elsevier Science Inc.