N-acetyl-L-cysteine abolishes the bromoethylamine-induced choline incorporation into renal papillary tissue.

The role of regenerative processes in the protective effect of N-acetyl-L-cysteine (NAC) against bromoethylamine-induced renal papillary necrosis was assessed in rats given bromoethylamine (BEA)(1.2 mmol/kg), N-acetylcysteine (6 mmol/kg), or N-acetyl-cysteine plus BEA. Renal papillary slices were dissected after 15 hours of treatment, and 14C-choline incorporation into total phospholipid, lysophosphatidylcholine, sphingomyelin, and phosphatidylcholine was measured. Bromoethylamine elicited an increase in the incorporation of 14C-choline into choline-containing phospholipid, an effect that was abolished when N-acetylcysteine was administered prior to bromoethylamine. These studies indicate that the defensive mechanism of N-acetylcysteine against bromoethylamine-induced renal papillary necrosis is not related to regenerative processes and that N-acetylcysteine abolishes the bromoethylamine-induced choline incorporation into papillary phospholipid.

Effect of different amino acidic pretreatments that protect the kidney against papillary necrosis induced by bromoethylamine on differential distribution of renal nonprotein sulfhydryls.

Content of nonprotein sulfhydryls (NPSH) was found to be higher in rat renal cortex than in external medulla and papilla. Administration of bromoethylamine (BEA), at a dose that produces extensive papillary necrosis and minor effects in the other renal segments, induced a significant reduction in NPSH levels of renal cortex and external medulla, with no changes in the papilla. Treatment with N-acetyl-L-cysteine (NAC) elicited an increase in papillary NPSH and a decrease in the cortex, with opposite changes being observed with an amino acid mixture of glutamine, glycine, and cystine (AM). Similar results were found in animals pretreated with NAC or AM prior to BEA intoxication. These pretreatments protect the cortex, external medulla, and papilla from the necrosis induced by BEA. It is suggested that protection of BEA-induced renal necrosis by NAC or AM pretreatments might be due to different mechanisms, with NPSH playing direct or indirect roles, respectively.

Sulfur-containing amino acids that increase renal glutathione protect the kidney against papillary necrosis induced by 2-bromoethylamine.

Papillary necrosis was observed in the kidneys of rats, 72 h after receiving a single injection of bromoethylamine (BEA). This effect was associated with renal glutathione (GSH) depletion 1 h after the administration of BEA. Stimulation of renal GSH synthesis by pretreatment of the animals either with glutamine + glycine + cystine or N-acetyl-L-cysteine was attempted. Low doses of these precursors administered previously to BEA, respectively, decreased or abolished the GSH depletion. Nevertheless, both pretreatments failed to modify the magnitude of renal papillary necrosis. High doses of these precursors did not modify the BEA-induced GSH depletion, but they significantly increased GSH levels 24 h after BEA administration. At this time, although a smaller intensity of renal papillary necrosis was observed with the amino acid mixture pretreatment, N-acetyl-L-cysteine pretreated rats showed no papillary necrosis. It is suggested that the observed protective effects against BEA-induced renal papillary injury may be ascribed in some measure, to a mechanism independent of GSH.