{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:49:06Z","timestamp":1783421346005,"version":"3.54.6"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infertility induced by anti-cancer treatments pose a major concern for cancer survivors. Doxorubicin (DXR) has been previously shown to exert toxic effects on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we studied its potential effect in reducing DXR-induced testicular toxicity. Male mice were injected with 5\u200amg\/kg DXR, 100\u200amg\/kg DEX, combination of both or saline (control) and sacrificed either 1, 3 or 6 months later. Testes were excised and further processed. Glutathione and apoptosis assays were performed to determine oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effects of the drugs on testicular histology and on spermatogonial reserve. DXR and the combined treatment induced a striking decline in testicular weight. DEX prevented DXR-induced oxidative stress, but enhanced DXR-induced apoptosis within the testes. Furthermore, the combined treatment depleted the spermatogonial reserve after 1 month, with impaired recovery at 3 and 6 months post-treatment. This resulted in compromised sperm parameters, testicular and epididymal weights as well as significantly reduced sperm motility, all of which were more severe than those observed in DXR-treated mice. The activity of DEX in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR exacerbates DXR-induced testicular toxicity.<\/jats:p>","DOI":"10.1530\/rep-15-0129","type":"journal-article","created":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T21:23:55Z","timestamp":1441142635000},"page":"357-366","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":30,"title":["Dexrazoxane exacerbates doxorubicin-induced testicular toxicity"],"prefix":"10.1093","volume":"150","author":[{"given":"Mattan","family":"Levi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moran","family":"Tzabari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naphtali","family":"Savion","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"The Goldschleger Eye Research Institute Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"Institute of Oncology Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"Sackler Faculty of Medicine Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salomon M","family":"Stemmer","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"The Goldschleger Eye Research Institute Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"Institute of Oncology Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"Sackler Faculty of Medicine Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Shalgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irit","family":"Ben-Aharon","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"The Goldschleger Eye Research Institute Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"Institute of Oncology Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"},{"name":"Sackler Faculty of Medicine Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel 1 Sheba Medical Center, Tel Hashomer 52621, Israel 2 Davidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, Israel 3 Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,10,1]]},"reference":[{"key":"2026010712431831600_bib1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0027-5107(83)90133-1","article-title":"Induction of sister-chromatid exchanges by chemotherapeutic drugs in spermatogonia of mice: effects of procarbazine, adriamycin, cyclophosphamide and mitomycin C","volume":"108","author":"Abraham","year":"1983","journal-title":"Mutation Research"},{"key":"2026010712431831600_bib2","first-page":"155171","article-title":"Catalytic inhibitors of DNA topoisomerase 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