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

Abstract

Abstract Dexamethasone, a synthetic glucocorticoid drug, is widely used as an anti-inflammatory/anti-allergic agent worldwide. Several previouse studies suggested that in the inflammatory or enriched free radical condition, Dexamethasone directly bind to DNA leading to DNA brekage/remodeling and subsequently cancer or other DNA breakage related disorders. So, for the first time, we computationally and experimentally investigated the interaction of 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, interaction of the drug with antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase 4, glutathione reductase was investigated by molecular docking methods. Interestingly, our in-vitro study demonstraded that dexamethasone binds to DNA by binding energy of -5.35 kcal/mol. Our study also indicatd that dexamethasone/DNA interaction lead to no DNA breakage while, its combination with the mineral supplies cause to DNA damage/breakage. This results are consistent with our Docking study that indicated dexamethasone stungly bind to DNA and the catalytic site of glutathione peroxidase 4, FAD-binding site of the glutathione reductase, the active site of the superoxide dismutase and NADPH binding residues of the catalase enzyme. Therefore, we hypothesis that Dexamethasone may indirectly make DNA damages by inhibiting antioxidant defense enzymes and causing oxidative stress in cells.