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    STUDIA BIOLOGIA - Issue no. 1 / 2004  
         
  Article:   ASPECTE HISTOPATOLOGICE ALE TOXICITĂŢII PANCREATICE A UNUI AGENT ALCHILANT ANTITUMORAL (CISPLATIN) LA ŞOBOLANII ALBI WISTAR DE V┬RSTE DIFERITE.

Authors:  CRISTINA PAŞCA, VICTORIA-DOINA SANDU.
 
       
         
  Abstract:  Histopathological Aspects of the Toxicity of an Antitumour Alkylating Agent (Cisplatin) on the Pancreas of White Wistar Rats of Different Ages. Cisplatin is an anticancer drug, more exactly an alkylating agent belonging to the family of platinum-containing products, widely used in the chemotherapy of many types of malignant diseases in humans. Unfortunately, according to the previous studies concerning its side effects, this drug has an antitumour activity correlated with a significant toxicity on different vital organs, consisting of the appearance of many and serious structural and functional alterations, which, sometimes, can endanger the life of the patient. Cisplatin has a significant toxicity on the whole digestive system (digestive tube and glands), which, so far, has been just tangentially investigated. Therefore, our researches intended to evaluate the histological and functional alterations induced by a single therapeutic dose of Cisplatin on the pancreas in puberal and mature white Wistar rats. Our results demonstrated that this antitumour drug, in monochemotherapy, has a moderate toxic effect on the rat pancreas, depending on the age of the rats, the most sensitive being the puberal individuals, in which the destructive processes appeared and got worse more quickly, and affected more seriously the structure of the pancreas. The toxic effect consisted of the appearance of certain histological modifications which affected both the cellular and vascular components of the organ. But, the histopathological alterations, both at the level of the exocrine and endocrine secretory units, seem to be due (induced and aggravated owing) to the grave circulatory disturbances (blood stasis, congestion, oedemas, intravascular coagulation phenomena) and thrombocytopenia, which determined a deficient supply with oxygen and nutritive substances, and an accumulation of some toxic metabolic products. The exocrine units (or acini) seem to be more sensitive than the islets of Langerhans. They appeared affected by an obvious diffuse oedema correlated with a serious perturbance of the intraacinar and intraductal transit of the pancreatic fluid. Besides, many and abundant lymphocyte and granulocyte infiltrations could be observed, especially perivascularly, around the pancreatic acini. The endocrine units of the pancreas (islets of Langerhans) were a little more resistant, the toxic action of Cisplatin determining only a transitory and discrete oedema and intravascular coagulation phenomena correlated with a moderate granulo-vacuolar dystrophy, and zonal necrosis processes. In addition, the destructive processes at the level of the islets of Langerhans were not associated with serious perturbation of the secretions of insulin and/or glucagon and, thus, the level of glucose in the blood was not significantly affected. Fortunately, both in the puberal and mature rats, the histological alterations induced by this dose of Cisplatin, administered in monochemotherapy, although perturbed both the exocrine and endocrine units of the pancreas, had no irreversible character, as at the end of the experimental period, without any protective or regenerative treatment, an obvious natural recovery process could be observed.  
         
     
         
         
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