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Potential anti-genotoxic effect of sodium butyrate to modulate induction of DNA damage by tamoxifen citrate in rat bone marrow cells

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Abstract

Sodium butyrate (SB) is one of the histone deacetylase inhibitors (HDACi’s) that is recently evidenced to have a prooxidant activity and an ability to reduce hydrogen peroxide-induced DNA damage. Since the majority of estrogen receptor positive breast cancer patients are treated with tamoxifen citrate (TC), which exerts well established oxidative and genotoxic effects, thus the basic objective of this study is to determine whether SB could ameliorate or curate tamoxifen citrate-induced oxidative DNA damage and genotoxic effect in vivo through up-regulation of some antioxidant enzymes. The individual and combined effects of SB and TC have been examined on rat bone marrow cells, using Micronucleus assays (MN), Comet assay, DNA fragmentation, expression of some antioxidant genes using Real time-PCR and finally, oxidative stress analysis. SB significantly increased the mitotic activity (P < 0.05), while TC induced marked micronuclei and oxidative DNA damage, in the SB post-treatment group, the combination of SB (300 mg/kg) and TC (40 mg/kg) was able to decrease the induction of MN and oxidative DNA damage through up-regulation of Cat, Sod and Gpx1 genes significantly at (P < 0.05) more efficiently than that in the SB pre-treatment one. Therefore, we postulate that SB can be used therapeutically in combination with TC treatment to modulate TC genotoxic effect by reducing its oxidative stress, and thus being an appropriate agonist agent to combine with TC than each compound alone.

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Acknowledgements

This work was supported by Faculty of Science and Cairo University. I would like to thank Dr/Hanan Saleh for being a useful guide in measuring different oxidative stress markers and assessing statistics.

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All the work of the present study is my own effort.

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El-Shorbagy, H.M. Potential anti-genotoxic effect of sodium butyrate to modulate induction of DNA damage by tamoxifen citrate in rat bone marrow cells. Cytotechnology 69, 89–102 (2017). https://doi.org/10.1007/s10616-016-0039-2

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