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Protection of mouse bone marrow from etoposide-induced genomic damage by dexrazoxane
Sabry M Attia1, Alaa A Al-Anteet, Nouf M Al-Rasheed
1Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. attiasm@yahoo.com
Purpose:
The objective of the current investigation is to determine whether non-toxic doses of the catalytic topoisomerase-II inhibitor, dexrazoxane, have influence on the genomic damage induced by the anticancer topoisomerase-II poison, etoposide, on mice bone marrow cells.
Method:
The scoring of micronuclei, chromosomal aberrations, and mitotic activity were undertaken as markers of cyto- and genotoxicity. Oxidative damage markers such as reduced glutathione and lipid peroxidation were assessed as a possible mechanism underlying this amelioration.
Results:
Dexrazoxane pre-treatment significantly reduced the etoposide-induced micronuclei formation, chromosomal aberrations, and also the suppression of erythroblast proliferation in bone marrow cells of mice. These effects were dose dependent. Etoposide induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation and reduction in the reduced glutathione level. Prior administration of dexrazoxane ahead of etoposide challenge ameliorated these biochemical markers.
Conclusion:
Based on our data presented, strategies can be developed to decrease the etoposide-induced genomic damage in normal cells using dexrazoxane.
Insights
Dexrazoxane, a topoisomerase-II inhibitor, significantly reduces etoposide-induced genomic damage and oxidative stress in mouse bone marrow cells. This finding supports strategies for protecting normal cells from chemotherapy side effects.
Area of Science:
- Pharmacology
- Genotoxicology
- Cancer Research
Background:
- Etoposide is an anticancer drug that functions as a topoisomerase-II poison.
- Chemotherapy can induce genomic damage in normal cells.
- Dexrazoxane is a catalytic topoisomerase-II inhibitor.
Purpose of the Study:
- To investigate the protective effects of dexrazoxane against etoposide-induced genomic damage.
- To determine if dexrazoxane influences oxidative stress markers.
Main Methods:
- Assessing micronuclei formation, chromosomal aberrations, and mitotic activity as genotoxicity markers.
- Measuring reduced glutathione and lipid peroxidation to evaluate oxidative damage.
- Utilizing mouse bone marrow cells for experimental analysis.
Main Results:
- Dexrazoxane pre-treatment dose-dependently reduced etoposide-induced micronuclei and chromosomal aberrations.
- Dexrazoxane ameliorated etoposide-induced suppression of erythroblast proliferation.
- Dexrazoxane mitigated etoposide-induced oxidative stress markers, including lipid peroxidation and reduced glutathione levels.
Conclusions:
- Dexrazoxane effectively reduces etoposide-induced genomic damage in normal cells.
- The protective mechanism may involve the amelioration of oxidative stress.
- Strategies using dexrazoxane can be developed to minimize chemotherapy-related genotoxicity.
