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Evaluation of dexamethasone and its combination with mineral supplements on the DNA compactness/breakage and the efficiency of antioxidant defense enzymes

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Abstract

Objective

Dexamethasone, a synthetic glucocorticoid drug, is widely used as an anti-inflammatory/anti-allergic agent worldwide. Several previous studies suggested that in the inflammatory or enriched free radical condition, Dexamethasone directly binds to DNA leading to DNA breakage/remodeling and subsequently cancer or other DNA breakage-related disorders.

Methods

So, for the first time, we computationally and experimentally investigated the interaction of the Dexamethasone drug, alone and in combination with H2O2, ascorbic acid, iron, and copper, with a routine supercoiled plasmid DNA. In the next step, the intrinsic DNA binding constant (kd) was calculated using UV absorption titration method via Dexamethasone interaction with calf thymus DNA (ctDNA). Also, the interaction of the drug with antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase 4, and glutathione reductase was investigated by molecular docking methods.

Results

Interestingly, our in-vitro study demonstrated that dexamethasone binds to DNA by binding energy of −5.35 kcal/mol. Our study also indicated that dexamethasone/DNA interaction leads to no DNA breakage while its combination with the mineral supplies causes DNA damage/breakage. These results are consistent with our Docking study that indicated dexamethasone strongly binds to DNA and the catalytic site of glutathione peroxidase 4, the FAD-binding site of the glutathione reductase, the active site of the superoxide dismutase, and NADPH binding residues of the catalase enzyme.

Conclusions

Therefore, we hypothesize that Dexamethasone may indirectly cause DNA damage by inhibiting antioxidant defense enzymes and causing oxidative stress in cells.

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Acknowledgements

We wish to thank the Zonguldak Bulent Ecevit University Scientific Research Commission for supporting our study through project grant no. 2018-50737594-01.

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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Sciences, Zonguldak Bulent Ecevit University, Zonguldak, Turkey

    Cagla Aslan & Ibrahim Arman

  2. Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran

    Mohsen Nabi-Afjadi

  3. Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Hamidreza Zalpoor

  4. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Hamidreza Zalpoor

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  1. Cagla Aslan
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  2. Ibrahim Arman
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Contributions

IA participates in the design and interpretation of the studies, and the review of the manuscript, CA, MNA, and HZ conducted the experiments and wrote the manuscript, and all images were drawn. IA  and MNA edited the manuscript and supervised it.

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Correspondence to Ibrahim Arman or Mohsen Nabi-Afjadi.

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Aslan, C., Arman, I., Nabi-Afjadi, M. et al. Evaluation of dexamethasone and its combination with mineral supplements on the DNA compactness/breakage and the efficiency of antioxidant defense enzymes. Toxicol. Environ. Health Sci. 15, 207–215 (2023). https://doi.org/10.1007/s13530-023-00174-9

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