Author/Editor     Zupančič, Daša
Title     Zaščitna vloga melatonina pri poškodbi in obnovi urotelija po delovanju ciklofosfamida
Type     monografija
Place     Ljubljana
Publisher     Univerza v Ljubljani, Medicinska fakulteta
Publication year     2006
Volume     str. 140
Language     slo
Abstract     Cyclophosphamide is used, alone or in combination with other chemotherapeutic agents, for treatment of numerous neoplastic diseases. The side effects of cyclophosphamide include life-threatening hemorrhagic cystitis. In rats, a single intraperitoneal dose of cyclophosphamide causes cystitis, which represents an experimental model for investigating damaged urinary bladder. Cancer treatment usually demands repeated doses of cyclophosphamide, but non-cancerous changes caused by repeated doses of cyclophosphamide have not yet been investigated. Furthermore, it has recently been shown, that melatonin ameliorates bladder damage induced by a single dose of cyclophosphamide. The aim of this work was therefore to study the role of melatonin during urothelial damage, repair, hyperplasia development and restoration of normal three-layer urothelium after a single dose of cyclophosphamide. For this purpose we used light and electron microscopy, immunohistochemistry and western blotting. We applied the same methods for investigation of non-cancerous urothelial changes after repeated doses of cyclophosphamide and the role of melatonin during these changes. Our previous study showed that during cyclophosphamide induced urothelial damage the urothelial cells express inducible nitric oxide synthase (iNOS). Numerous reports indicate that melatonin regulates iNOS expression; consequently we also examined iNOS expression in urothelial cells after single and repeated doses of cyclophosphamide and after co-treatment with melatonin. We discovered that after a single dose of cyclophosphamide and melatonin, melatonin protected urothelial cells from necrotic changes and also decreased their apoptosis. Melatonin therefore prevented the extensive loss of urothelial cells from the urothelium and the exposure of basal lamina. (Abstract truncated at 2000 characters)
Descriptors     BLADDER
CYCLOPHOSPHAMIDE
UROTHELIUM
MELATONIN
KERATIN
RATS, INBRED F344
MEMBRANE PROTEINS
MICROSCOPY, ELECTRON
BLOTTING, WESTERN
APOPTOSIS
NITRIC-OXIDE SYNTHASE