{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:21:44Z","timestamp":1778286104180,"version":"3.51.4"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T00:00:00Z","timestamp":1193616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Melatonin was recently shown to have protective effects against cyclophosphamide (CP)\u2010induced 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\u2010weeks 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\u2003mg\/kg; CP group) or melatonin (10\u2003mg\/kg) with CP (Mel + CP group). Melatonin co\u2010treatment 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\u2010treatment suddenly dropped and therefore the development of hyperplasia was prevented. Melatonin co\u2010treatment with CP also resulted in earlier differentiation of superficial urothelial cells. Melatonin seems to have protective effect against CP\u2010induced 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.<\/jats:p>","DOI":"10.1111\/j.1600-079x.2007.00530.x","type":"journal-article","created":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T09:41:50Z","timestamp":1193650910000},"page":"299-306","source":"Crossref","is-referenced-by-count":22,"title":["Effect of melatonin on apoptosis, proliferation and differentiation of urothelial cells after cyclophosphamide treatment"],"prefix":"10.1111","volume":"44","author":[{"given":"Da\u0161a","family":"Zupan\u010di\u010d","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristijan","family":"Jezernik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaj","family":"Vidmar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,10,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)41173-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(79)90222-3"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2964(81)90261-9"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1997.tb03745.x"},{"key":"e_1_2_6_6_2","first-page":"247","article-title":"Involvement of nitric oxide in the pathogenesis of cyclophoshamide\u2010induced hemorrhagic cystitis","volume":"150","author":"Souza\u2010filho MVP","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-003-0398-y"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000154344.80669.e3"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2005.00304.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2006.00407.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2007.00432.x"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000049649.80549.17"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2004.00131.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000145891.35810.56"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-004-0822-1"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2004.00202.x"},{"key":"e_1_2_6_17_2","first-page":"1577","article-title":"Cyclophosphamide and urinary bladder toxicity","volume":"21","author":"Philips FS","year":"1961","journal-title":"Cancer Res"},{"key":"e_1_2_6_18_2","first-page":"44","article-title":"A light and electron microscopic study of the effects of a single dose of cyclophosphamide on various organs in the rat","volume":"16","author":"Koss LG","year":"1967","journal-title":"Lab Invest"},{"key":"e_1_2_6_19_2","first-page":"116","article-title":"Repair of rat urinary bladder epithelium following injury by cyclophosphamide","volume":"8","author":"Locher GW","year":"1970","journal-title":"Investig Urol"},{"key":"e_1_2_6_20_2","first-page":"89","article-title":"Scanning electron microscopy of cyclophosphamide\u2010induced hyperplasia of the rat urinary bladder","volume":"44","author":"Fukushima S","year":"1981","journal-title":"Lab Invest"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1065-6995(03)00175-6"},{"key":"e_1_2_6_22_2","first-page":"279","article-title":"Cell kinetics of mouse urinary bladder epithelium. 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