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    STUDIA BIOLOGIA - Issue no. 2 / 2000  
         
  Article:   HISTOLOGICAL AND ULTRASTRUCTURAL INJURIES IN THE RAT KIDNEY AFTER EXPOSURE TO CISPLATIN.

Authors:  CRISTINA PAŞCA, VIOREL MICLĂUŞ, CONSTANTIN CRĂCIUN, ERIKA KIS, VICTORIA-DOINA SANDU, VERONICA CRĂCIUN, IONEL PAPUC, CRISTIAN MUNTEANU.
 
       
         
  Abstract:  Cisplatin, a platinum compound, is an alkylating agent with a marked antitumour activity, that has been extensively and successfully applied in the chemotherapy of several types of cancer (testicular, ovarian, pulmonary etc). Unfortunately, it has a significant hematologic and nonhematologic toxicity, especially nephrotoxicity. The tissue injury and repair in the rat kidney induced by this anticancer drug are still incompletely known; therefore, we tried to emphasise the histological and ultrastructural modifications induced by some therapeutic doses of Cisplatin on the rat kidney. Our researches demonstrated that the lesions were very grave, affected wide areas and progressively and significantly grew worse during the experiment. They consisted of the appearance of a marked swelling of the renal tubules, especially between the cortex and medulla, a distension of the epithelial cells, the cytoplasm of which appeared homogeneous and in some areas the epithelium was atrophied or detached. In addition, it could be noticed a granular material inside the renal tubules (because of the necrosis processes of the epithelial cells), a proliferation of mesangial and endothelial cells, an accumulation of certain circulating elements (polymorphonuclears, monocytes, lymphocytes) in the capillary lumen. The mesangial and monocytic interposition determined the parietal thickening and the striking "double outline" aspect of the basement membrane. Electron microscopy studies showed that Cisplatin induced grave nuclear alterations, a complete vacuolisation of the apical cytoplasm, intracellular lysis, while the mitochondria were swollen and had a rarefied matrix. Many epithelial cells in the uriniferous tubules had a seriously affected brush border, the microvilli being swollen and destroyed here and there, and the basal infoldings appeared hypertrophied. An increase of the mesangial matrix, with an obvious expansion in the capillary loops, determined the "double outline" aspect of the basement membrane which was found in light microscopy investigations. Besides, a pronounced cellularity of the glomeruli appeared, which was due to mesangial cell proliferation and especially to monocytic infiltration. Monocytes appeared in the mesangial zone, between the basement membrane and the endothelium along with mesangial cells, or in the lumen of some capillaries. Deposits of granular structure were found in the subendothelial area.  
         
     
         
         
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