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The Effect of Arsenic Trioxide on All-trans Retinoic Acid Binding to Human Serum Albumin

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Abstract

Tretinoin or All-trans retinoic acid (ATRA) is an efficient medication in leukemia treatment. Arsenic trioxide (ATO) significantly improves the effectiveness of ATRA. In this study, the effect of ATO on ATRA binding to human serum albumin (HSA) was investigated. Fluorescence and UV-Vis spectroscopy and equilibrium dialysis technique were used to determine ATRA binding to HSA in the presence and absence of ATO and of two compounds, warfarin and ibuprofen, specific for binding to HSA sites I and II, respectively (“site markers”). The association constants for ATRA binding and the number of binding sites as well as the thermodynamic parameters of complex formation, were obtained at different temperatures. Fluorescence results showed a static quenching mechanism for ATRA binding to HSA. The calculated thermodynamic parameters revealed that the binding reaction is a spontaneous and exothermic process and also that hydrogen bonds and van der Waals forces have a central role in the binding of ATRA to HSA. Competitive experiments showed that none of markers seriously prevents ATRA binding to HSA. Interestingly, the fluorescence and equilibrium dialysis data showed that ATO increases the binding of ATRA to HSA, and converts the binding mode of ATRA from mainly hydrogen bonding to include hydrophobic interactions as well. These results suggest that ATO can prevent the metabolism of ATRA and keep it in the blood for longer by increasing the binding of ATRA to HSA.

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Acknowledgements

The Author would like to express her profound gratitude to Professor Ali Mostafaei and Professor Reza Khodarahmi for permitting the use of their laboratories equipment. The Author also appreciates the help of the Deputy for Research and Technology, Kermanshah University of Medical Sciences in supporting this work (grant number 94523).

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Correspondence to Soghra Bagheri.

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Bagheri, S. The Effect of Arsenic Trioxide on All-trans Retinoic Acid Binding to Human Serum Albumin. J Fluoresc 29, 1277–1283 (2019). https://doi.org/10.1007/s10895-019-02458-1

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