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Modulation of doxorubicin-induced genotoxicity by squalene in Balb/c mice
Bhilwade Hari Narayan1, Naoto Tatewaki, Vijayasree Vayalanellore Giridharan
1Niigata University of Pharmacy & Applied Life Sciences, Department of Functional and Analytical Food Sciences, Higashijima 738-1, Niigata 956-8603, Japan.
Abstract:
The present study aims to evaluate the protective effect of squalene against the genotoxicity of the chemotherapeutic agent doxorubicin (Dox) using two genotoxicity assays, the micronucleus assay and the comet assay. Different groups of mice were fed squalene at the doses of 1 and 4 mmol g(-1) body weight (100 or 400 μl as squalene oil) either at 4 h before or 1 h after Dox (20 mg kg(-1)) treatment. 24 h after the Dox treatment, bone marrow erythrocytes were evaluated for the incidence of micronuclei, and the induced DNA strand breaks were examined in heart tissue by the alkaline comet assay. As expected, Dox significantly induced micronuclei in polychromatic (immature) erythrocytes, as well as in total erythrocytes. The frequency of Dox-induced micronucleated erythrocytes was significantly reduced in the mice treated with squalene both before and after Dox administration. Squalene itself obviously did not induce any micronuclei in bone marrow erythrocytes. The comet assay also demonstrated a significant increase in DNA damage, especially DNA single strand breaks in the Dox-treated group of mice as compared to the control. The Dox-induced DNA damage was also effectively reduced by squalene when it was administered either before or after the Dox treatment. Squalene did not induce any significant DNA damage by itself. Compared to the pre-treatment of squalene, post treatment gave rise to more effective prevention against Dox-induced DNA damage. The data suggest that the complimentary use of squalene with Dox will be beneficial to reduce the adverse effect of Dox in cancer chemotherapy, such as the increased incidence of undesirable mutagenic side effects.
Insights
Squalene protects against doxorubicin-induced genotoxicity in mice. This natural compound reduces DNA damage and micronuclei formation, suggesting its use in cancer chemotherapy to mitigate mutagenic side effects.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Doxorubicin (Dox) is a potent chemotherapeutic agent.
- Doxorubicin induces genotoxicity, leading to adverse mutagenic side effects.
- Squalene is a natural compound with potential protective properties.
Purpose of the Study:
- To evaluate the protective effect of squalene against doxorubicin-induced genotoxicity.
- To assess squalene's impact on DNA damage and micronuclei formation.
- To determine optimal squalene administration timing relative to doxorubicin treatment.
Main Methods:
- Genotoxicity was assessed using the micronucleus assay in bone marrow erythrocytes.
- DNA strand breaks were evaluated in heart tissue via the alkaline comet assay.
- Mice were treated with squalene (1 and 4 mmol/g) before or after doxorubicin (20 mg/kg).
Main Results:
- Doxorubicin significantly increased micronuclei formation and DNA strand breaks.
- Squalene administration, both before and after doxorubicin, significantly reduced these genotoxic effects.
- Squalene alone did not induce genotoxicity.
- Post-treatment with squalene showed more effective prevention against doxorubicin-induced DNA damage compared to pre-treatment.
Conclusions:
- Squalene exhibits significant protective effects against doxorubicin-induced genotoxicity.
- Complementary use of squalene with doxorubicin may reduce chemotherapy's mutagenic side effects.
- Squalene represents a promising adjuvant therapy to enhance the safety profile of doxorubicin chemotherapy.
