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Effect of melatonin on apoptosis, proliferation and differentiation of urothelial cells after cyclophosphamide treatment
Author(s) -
Zupančič Daša,
Jezernik Kristijan,
Vidmar Gaj
Publication year - 2008
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00530.x
Subject(s) - urothelium , melatonin , apoptosis , urothelial cell , regeneration (biology) , endocrinology , medicine , hyperplasia , oxidative stress , andrology , biology , microbiology and biotechnology , urinary system , biochemistry
Melatonin was recently shown to have protective effects against cyclophosphamide (CP)‐induced hemorrhagic cystitis (HC) by diminishing bladder oxidative stress. HC is accompanied by destruction of the bladder urothelium and followed by apoptosis and rapid regeneration via proliferation and differentiation of urothelial cells, reaching complete restoration of normal urothelium in three weeks. Therefore, the effect of melatonin on apoptosis, proliferation and differentiation of urothelial cells, during destruction and regeneration of the urothelium three‐weeks after a single dose CP treatment, was studied. F344 male rats were injected intraperitoneally with saline (control group) or melatonin (Mel group) or a single dose of CP (100 mg/kg; CP group) or melatonin (10 mg/kg) with CP (Mel + CP group). Melatonin co‐treatment with CP significantly reduced apoptosis and increased proliferation of urothelial cells at day 1 and thus prevented extensive loss of cells from the urothelium. However, proliferation indices at days 4 and 7 after melatonin and CP co‐treatment suddenly dropped and therefore the development of hyperplasia was prevented. Melatonin co‐treatment with CP also resulted in earlier differentiation of superficial urothelial cells. Melatonin seems to have protective effect against CP‐induced urothelial damage and a favorable impact on regeneration and restoration of normal urothelium, since it reduces the number of apoptotic and proliferating urothelial cells and results in their earlier differentiation.