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  • Melatonin prevents the development of hyperplastic urothelium induced by repeated doses of cyclophosphamide
    Zupančič, Daša ; Vidmar, Gaj ; Jezernik, Kristijan
    Repeated cyclophosphamide (CP) chemotherapy increases the risk of developing bladder cancer, which could be due to the extremely rapid proliferation of urothelial cells observed in hyperplastic ... urothelium induced by CP treatment. We investigated the effect of melatonin on the development of urothelial hyperplasia induced by repeated CP treatment. Male ICR mice were injected withCP (150 mg/kg) or melatonin (10 mg/kg) with CP once a week for 3, 4 and 5 weeks. Transmission and scanning electron microscopy, immunohistochemistry andWestern blot analysis were used to study the ultrastructure, apoptosis, proliferation and differentiation of urothelial cells. Repeated doses of CP caused the development of hyperplastic urothelium with up to ten cell layers and increased proliferation and apoptotic indices regarding Ki-67 and active caspase-3 immunohistochemistry, respectively. Scanning electron microscopy observations, cytokeratin and asymmetrical unit membrane immunohistochemistry and Western blot analysis showed a lower differentiation state of superficialurothelial cells. Melatonin co-treatment prevented the development of hyperplastic urothelium, statistically significantly decreased proliferation and apoptotic indices after four and five doses of CP and causedhigher differentiation state of superficial urothelial cells.
    Source: Virchows Archiv. - ISSN 0945-6317 (Letn. 454, št. 6, 2009, str. 657-666)
    Type of material - article, component part
    Publish date - 2009
    Language - english
    COBISS.SI-ID - 25923545
    DOI

source: Virchows Archiv. - ISSN 0945-6317 (Letn. 454, št. 6, 2009, str. 657-666)
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