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    STUDIA BIOLOGIA - Issue no. 2 / 2001  
         
  Article:   STRUCTURAL AND ULTRASTRUCTURAL MODIFICATIONS INDUCED BY TWO THERAPEUTIC DOSES OF CIS-DIAMMINEDICHLOROPLATINUM(II) (CISPLATIN) ON SOME LYMPHOID ORGANS IN WHITE WISTAR RATS.

Authors:  CRISTINA PAŞCA, CONSTANTIN CRĂCIUN, ERIKA KIS.
 
       
         
  Abstract:  cis-Diamminedichloroplatinum(II) (cis-DDP or Cisplatin) is an antineoplastic agent with vast therapeutic potential, especially against solid tumours, such as bladder, ovarian and testicular carcinomas. The major side effects of this anticancer drug are its nephrotoxicity and myelotoxicity. Our researches tried to establish the histological and ultrastructural modifications induced by two different doses of Cisplatin (10 and 20 mg/m2 body surface) on some lymphoid organs, particularly on the thymus and spleen, in concordance with the moment of the sacrification. The light and electron microscopy evidenced that both these therapeutic cytostatic doses (especially the high dose) had a significant toxic effect both on the cellular component (lymphocyte populations and reticulo-epithelial cells) and on the vascular component in these organs. The toxic action of Cisplatin on the lymphocytes was determined by its antimitotic activity, correlated with a drastic necrobiotic, necrotic and a moderate apoptotic effect. Sensitivity of the lymphocytes depended on their age, the most affected having been the lymphoblasts. Cisplatin induced a marked depletion of the thymic lobules and splenic nodules. Ultrastructurally, in the thymus, we could see that a very large number of lymphocytes was affected by some degenerative processes as demonstrated by the appearance of many modified (retracted and pycnotic) nuclei, with a cortical hyperchromatosis, and many swollen and vacuolised mitochondria. In the spaces which were created by the lysis processes, a discrete collagen proliferation could be noticed. The degenerative processes seemed to affect a moderate number of epithelio-reticular cells, which had a vacuolised cytoplasm and modified nuclei and cellular organelles. The destructive processes were correlated with a moderately increased number of eosinophils and a large number of macrophages. According to the toxic effect of Cisplatin on the vascular component in the two lymphoid organs, we could see that it resulted in the appearance of a severe congestion and stasis correlated with a change of the vascular permeability which determined massive perivascular oedemas and even a few microhaemorrhages. All these morphopathological aspects appeared immediately, in both thymus and spleen, developed progressively and significantly especially in the rats treated with the high dose. Besides, in rats treated with 20 mg Cisplatin/m2 body surface we could notice a reactivation of the extramedullary hematopoiesis at the end of the experimental period.  
         
     
         
         
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