Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

Reproduction : the Official Journal of the Society for the Study of Fertility
Mattan LeviIrit Ben-Aharon

Abstract

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  mg/kg DXR, 100  mg/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 i...Continue Reading

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Citations

Mar 30, 2016·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Zhiru WangDesheng Zhu
Feb 21, 2019·PloS One·Marianne K O GrantBeshay N Zordoky
May 4, 2018·Oncotarget·Mattan LeviIrit Ben-Aharon
Oct 7, 2020·The FEBS Journal·Sabina Y van der ZandenJacques Neefjes

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