Melatonin prevents the development of hyperplastic urothelium induced by repeated doses of cyclophosphamide
| Autor: | Kristijan Jezernik, Daša Zupančič, Gaj Vidmar |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Antineoplastic Agents Apoptosis Biology Pathology and Forensic Medicine Urothelial Hyperplasia Melatonin Andrology Mice Cytokeratin Western blot Internal medicine medicine Animals Urothelium Antineoplastic Agents Alkylating Cyclophosphamide Molecular Biology Cell Proliferation Mice Inbred ICR Hyperplasia medicine.diagnostic_test Cell Biology General Medicine medicine.disease Ki-67 Antigen Endocrinology Immunohistochemistry Drug Screening Assays Antitumor Drug Antagonism Precancerous Conditions medicine.drug |
| Zdroj: | Virchows Archiv. 454:657-666 |
| ISSN: | 1432-2307 0945-6317 |
| DOI: | 10.1007/s00428-009-0765-3 |
| Popis: | 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 with CP (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 and Western 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 superficial urothelial 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 caused higher differentiation state of superficial urothelial cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink