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Dexrazoxane exacerbates doxorubicin-induced testicular toxicity
Mattan Levi1, Moran Tzabari1, Naphtali Savion2
1Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, IsraelThe Goldschleger Eye Research InstituteSheba Medical Center, Tel Hashomer 52621, IsraelInstitute of OncologyDavidoff Center, Rabin Medical Center, Beilinson Campus, 39 Jabotinski Street, Petah-Tiqva 49100, IsraelSackler Faculty of MedicineTel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Reproduction (Cambridge, England)
|September 3, 2015
Summary
Dexrazoxane (DEX) does not protect against Doxorubicin (DXR)-induced testicular toxicity in mice. Instead, combining DEX with DXR worsens sperm parameters and depletes the spermatogonial reserve, highlighting differing drug effects in testes versus the heart.
Area of Science:
- Reproductive Toxicology
- Oncology
- Pharmacology
Background:
- Anti-cancer treatments like Doxorubicin (DXR) can cause infertility in cancer survivors.
- Dexrazoxane (DEX) is known for cardioprotective effects, but its impact on testicular toxicity is unknown.
Purpose of the Study:
- To investigate the potential of Dexrazoxane (DEX) in mitigating Doxorubicin (DXR)-induced testicular toxicity.
- To evaluate the effects of DEX and DXR, alone and in combination, on male mouse reproductive health.
Main Methods:
- Male mice received DXR, DEX, a combination, or saline.
- Testicular tissues were analyzed at 1, 3, and 6 months post-treatment.
- Assays included glutathione and apoptosis for oxidative stress, and immunohistochemistry/confocal microscopy for histology and spermatogonial reserve.
Main Results:
- DXR and combined treatment significantly reduced testicular weight.
- DEX counteracted DXR-induced oxidative stress but increased DXR-induced apoptosis.
- The combined treatment severely depleted spermatogonial reserve and impaired sperm parameters and motility, exceeding DXR-only effects.
Conclusions:
- Dexrazoxane (DEX) activity in the testes differs from its cardioprotective role in cardiomyocytes.
- Combining DEX with Doxorubicin (DXR) exacerbates DXR-induced testicular toxicity and infertility.
- DEX is not recommended for mitigating DXR-induced male reproductive toxicity.
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