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    STUDIA BIOLOGIA - Issue no. 1 / 2003  
         
  Article:   NEFROTOXICITATEA NUROFENULUI SURPRINSĂ LA NIVEL STRUCTURAL ŞI ULTRASTRUCTURAL LA ŞOBOLANUL ALB WISTAR.

Authors:  CRISTINA PAŞCA, CONSTANTIN CRĂCIUN, MIHAELA IOANA DRIHA.
 
       
         
  Abstract:  Nephrotoxicity of Nurofen as Assessed at Structural and Ultrastructural Levels in White Wistar Rats. Nurofen, an antiinflammatory drug widely used in the therapy of many diseases in humans, has a lot of side effects which, often, are so grave that the health of the treated person can be seriously disturbed. Unfortunately, these side effects are not completely known. Our investigations demonstrated that Nurofen, administered in a dose of 250 mg/kg body weight for 35 days, has a significant nephrotoxicity, which could be clearly noticed after 10 days of treatment and which got worse constantly and progressively during the whole experimantal period. All the histopathological and ultrastructural alterations induced by this drug had not an irreversible character, a natural recovery phenomenon of the kidney being possible after the end of the treatment. By light microscopy studies, we could distinguish many histological modifications: an obvious glomerular stasis which affected wide areas and which was correlated with a swelling of the mesangial structures, the appearance of many lobulated glomerules in which we notice the presence of a rich PAS+ material placed at the level of the mesangium and Bowman space, a zonal interstitial nephritis. Besides, a few of altered glomerules were affected by caryopycnosis, atrophy and sclerosis processes. Zonally, both in cortex and medulla, an obvious disseminated intravascular coagulation phenomenon could be observed. Ultrastructurally, we could observe that the modifications induced by the treatment with Nurofen affected especially the cells at the level of proximal convoluted tubule. Thus, most nuclei of these nephrocytes had an abnormal shape and appeared pycnotic, retracted, hyperchromatic, with a peculiar disposition of the chromatin. The cytoplasm was seriously altered, more exactly it was intensely vacuolised, having wide lysis areas which were disposed apically. Among the cellular organelles the most sensitive in this treatment seemed to be the lysosomes - which were identified in an increased number, and the mitochondria ľ which, in most cases, became spherical, being swollen and greatly alterated, vacuolised, having a matrix and cristae seriously disturbed. Zonally, the nephrocytes had an obvious tendency to get a cuboidal or even squamous, flat shape, simultaneously losing their brush border or getting some polymorphous, swollen and seriously vacuolised microvilli. As a consequence of these grave alterations, in a few areas the apical pole of the nephrocytes appeared completely destroyed, the cytoplasm, nucleus and organelles being eliminated inside the lumina of the proximal convoluted tubule.  
         
     
         
         
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