Dexrazoxane has been approved to treat
anthracycline-induced
cardiomyopathy and extravasation. However, the effect of
dexrazoxane on
epirubicin-induced genetic alterations in germ cells has not yet been reported. Thus, the aim of this study was to determine whether
dexrazoxane modulates
epirubicin-induced genetic damage in the germ cells of male mice. Our results show that
dexrazoxane was not genotoxic at the tested doses. Furthermore, it protected mouse germ cells against
epirubicin-induced genetic alterations as detected by the reduction in disomic and diploid sperm, spermatogonial
chromosomal aberrations, and abnormal sperm heads. The attenuating effect of
dexrazoxane was greater at higher dose, indicating a dose-dependent effect. Moreover, sperm motility and count were ameliorated by
dexrazoxane pretreatment.
Epirubicin induced marked biochemical changes characteristic of oxidative DNA damage including elevated
8-hydroxy-2'-deoxyguanosine levels and reduction in
reduced glutathione. Pretreatment of mice with
dexrazoxane before
epirubicin challenge restored these altered endpoints. We conclude that
dexrazoxane may efficiently mitigate the
epirubicin insult in male germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and associated health risks. Thus, pretreating patients with
dexrazoxane prior to
epirubicin may efficiently preserve not only sperm quality but also prevent the transmission of genetic damage to future generations.