1H NMR Spectroscopic and Histopathological Studies on Propyleneimine-Induced Renal Papillary Necrosis in the Rat and the Multimammate Desert Mouse ( Mastomys natalensis)

Abstract

The renal papillary toxin, propyleneimine (PI), was administered at 20 or 30 μl/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 1H NMR spectroscopy of urine, renal histopathology, and urinary assays for alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyl transpeptidase ( γGT). 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 μl/kg PI and, although slight to moderate damage was observed at 30 μl/kg, PI-treated Mastomys showed substantially less RPN than either group of PI-treated rats. 1H 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 1H NMR-detected urinary biochemical effects of PI in all three models were similar. However, taurine concentrations were elevated in the urine of Mastomys 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.