THE EFFECT OF LONG-TERM ADMINISTRATION OF ASPIRIN AND SODIUM SACCHARIN ON THE RAT-KIDNEY

In a study primarily designed to evaluate the inhibitory effects of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-initiated and saccharin-promoted bladder carcinogenesis, significant renal lesions were observed. Thus, administration in the diet of aspirin and sodium saccharin to F344 male rats for 68 weeks resulted in significant lesions of the renal papilla. In contrast to the bladder, aspirin enhanced the frequency and severity of the proliferative action of sodium saccharin on the epithelium of the renal papilla (p < 0.05 compared to rats treated with either compound alone). The majority of rats administered the two chemicals together demonstrated moderate to severe urothelial hyperplasia of the renal papilla. Columnar metaplasia of the papillary epithelium also occurred frequently in rats fed the combination of chemicals. The rats treated with a combination of sodium saccharin and aspirin had a high incidence of renal papillary necrosis which was also present to a lesser extent among rats treated with aspirin only. Papillary calcification was also frequently observed in the rats fed the combination of aspirin and sodium saccharin. Sodium saccharin or aspirin alone reduced the light microscopic incidence and severity of rat nephropathy, a common finding in aging rats. It would appear that the hyperplastic and renal papillary toxic effects of aspirin and sodium saccharin are independent responses, and that the administration of the two chemicals together greatly accentuates these responses.