Pathologic analysis of chemical nephritis in rats induced by N-(3,5-dichlorophenyl)succinimide

The effects of N-(3,5-dichlorophenyl)succinimide (NDPS) administration to rats were studied by blood chemical, histopathologic, histochemical, and ultrastructural examinations. Administration of 5000 p.p.m. of NDPS induced severe damage of the kidneys, but did not affect other organs. Administration of 2500 p.p.m. of NDPS had little effect, even on the kidneys. Chemical analysis of the blood showed that the urea nitrogen level increased with the increase in the period of NDPS administration. Histopathologic examination showed intensive cell infiltration, mainly of lymphocytes, into the renal interstitium after NDPS administration for only 4 weeks. After NDPS administration for 12 weeks or more, typical interstitial nephritis was observed. Histochemical analysis showed that after only 1 week various enzymatic activities in the proximal convoluted tubules were markedly decreased whereas their activities in the distal convoluted tubules were relatively well preserved for at least 4 weeks. These results indicate that NDPS predominantly attacked the proximal convoluted tubules. After 4 weeks, the most prominent ultrastructural changes were seen in the proximal convoluted tubules where the epithelial cells lost their polarity and had a very abnormal arrangement. These cells showed well developed, edematous microvilli, poorly developed basal infoldings, swollen mitochondria of various sizes, aggregated beta-type glycogen granules, and debris of erythrocytes. Development of the endoplasmic reticulum, Golgi complex, ribosomes, and lysosomes was poor in the cytoplasm. These investigations indicate that NDPS affects the function of the proximal convoluted tubules. NDPS is a selective nephrotoxic substance. That is, it initially damages the proximal convoluted tubules, and subsequently causes interstitial nephritis. It is suggested that nephritis induced by NDPS is useful as a model of interstitial nephritis in man.