Experimental induction of renal papillary necrosis in laboratory rodents

Stephen Dana Lenz, Purdue University

Abstract

The nephrotoxicity of acetylsalicylic acid, antipyrine, aminopyrine, diphenylamine and L-triiodothyronine were investigated in laboratory rodents, with special emphasis on the induction of renal papillary necrosis. Of the five compounds tested, only diphenylamine induced total renal papillary necrosis in male Syrian hamsters. Morphologically the lesion was a bland coagulative necrosis of the renal papilla characterized by necrosis of the interstitial cells, vasa recta, thin limbs of Henle and collecting tubules. This lesion was most consistently induced within 24 hours after a single oral dose of 600 mg diphenylamine/kg and the lesion occurred in 50-90% of the test animals. Fasting and water deprivation increased the incidence of diphenylamine induced renal papillary necrosis in Syrian hamsters. Treatment with antioxidants (N,N$\sp\prime$-diphenyl-p-phenylenediamine, $\alpha$-tocopherol, or ascorbic acid) had no effect on the incidence of the lesion, nor did the induction of microsomal enzymes by phenobarbital. Ammonium chloride administration to Syrian hamsters prior to the administration of diphenylamine reduced the incidence of renal papillary necrosis in the face of markedly reduced water consumption. The initial ultrastructural lesion of diphenylamine induced renal papillary necrosis in male Syrian hamsters occurred within one hour of the administration of diphenylamine was cytoplasmic vacuolation of the endothelial cells of the ascending vasa recta in the proximal portion of the renal papilla followed by elevation of the basal plasma membrane, forming subendothelial vacuoles, and exposure of the basal lamina. Ultrastructural alterations in renal medullary interstitial cells were subsequent to the endothelial cell lesions, and consisted of reduction in amount of cytoplasm, separation of the cytoplasm into multiple small, thin projections surrounded by excessive basal lamina-like material. Degeneration and necrosis of interstitial cells and epithelial cells of the thin limbs of Henle and collecting tubules was subsequent to the endothelial cell injury. L-triiodo-thyronine induced the formation of randomly scattered, multinucleate syncytial cells within the renal cortical distal tubules of Sprague-Dawley rats, but not in Syrian hamsters or Mongolian gerbils. No renal lesions were observed in male Syrian hamsters administered acetylsalicylic acid, antipyrine, or aminopyrine.

Degree

Ph.D.

Advisors

Carlton, Purdue University.

Subject Area

Animal diseases|Veterinary services

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