The effect of glucose on doxorubicin and human hemoglobin interaction: Characterization with spectroscopic techniques

The application of doxorubicin (DOX), which is the most effective anticancer drug, is limited due to its cardiac toxicity. The study of DOX-hemoglobin (Hb) interaction has biochemical and toxicological importance. Understanding the Hb-DOX interaction in the presence of glucose (Glc), as the main blood sugar, can be advantageous for clinical implications. In this study, the structural changes imposed by DOX on Hb in the presence of various concentrations of Glc were investigated using different methods such as UV-Vis, fluorescence, and circular dichroism (CD) spectroscopy. The results obtained by the spectroscopic techniques revealed that the hyperchromic effect, which was observed after treating Hb with DOX, was relieved in the presence of Glc. Based on the results of fluorescence spectroscopy, some of the photons emitted from the tryptophan (Trp) residues were quenched due to DOX binding. Since the Trp residues were exposed, the intrinsic fluorescence of Hb increased but the residues might not have been competent for DOX binding anymore. The results of the CD technique demonstrated that the levels of the alpha-helix structure were significantly reduced when Hb was simultaneously treated with DOX and Glc. Thermal stability studies revealed that the melting temperature of Hb increased in the presence of Glc alone. However, the thermal stability of Hb decreased in the presence of Glc/DOX (combined). Since the concentration of Glc in diabetic patients is significantly higher than in healthy individuals, the toxic effects of DOX, due to its interaction with Hb, may be different in healthy and diabetic subjects.