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Dalcetrapib and reduced glutathione effect on hemoglobin S polymerization studied by NMR

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Abstract

The effects of dalcetrapib (dal) and reduced glutathione (GSH) on a hemoglobin S (HbS) polymerization process are quantitatively evaluated using proton (1H) magnetic relaxation. The HbS samples were obtained, using classical methods (centrifuging, decanting, and freezing–thawing cycles), starting from whole blood of voluntary patients suffering sickle cell disease (SCD). The transversal 1H magnetic relaxation time (T2) was determined at 36 °C using the Carr-Purcell-Meiboom-Gill (CPMG) experiment (echo time: 1000 μs, 1000 echoes, 90° and 180° pulses of equal amplitude, and with 5 μs and 10 μs of width respectively), and its temporal behavior was used to obtain the initial (T2i) and final (T2f) values of T2 as well as the delay time (td) of the HbS polymerization process. Both compounds showed an effect on the HbS polymerization process with increments of td in the 60% of the samples treated with GSH, as well as an increase of T2i and T2f in the 100% of the samples treated with dal. The changes in these parameters indicate, in both cases, an inhibition of the HbS polymerization processes.

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Acknowledgements

This work has been supported by the Belgian Development Cooperation through VLIR-UOS (Flemish Interuniversity Council-University Cooperation for Development) in the context of the Institutional University Cooperation program with Universidad de Oriente. The authors also wish to thank the MRI Centre of the University of New Brunswick in Canada, for the support received for the completion of this work.

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Authors and Affiliations

  1. Centro de Biofísica Médica, Universidad de Oriente, Patricio Lumumba S/N. CP: 90500, Santiago de Cuba, Cuba

    Lilian María Somoano Delgado, Manuel Arsenio Lores, Juan Carlos García & Fabian Tamayo Delgado

  2. Hartis Pharma, Nyon, Switzerland

    Joseph Eric Niesor & Anne Perez

  3. Hospital General “Dr. Juan Bruno Zayas Alfonso”, Santiago de Cuba, Cuba

    Inocente Rodriguez & Samuel Rosales

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  1. Lilian María Somoano Delgado
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  2. Manuel Arsenio Lores
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  3. Juan Carlos García
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Correspondence to Lilian María Somoano Delgado.

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Somoano Delgado, L.M., Lores, M.A., García, J.C. et al. Dalcetrapib and reduced glutathione effect on hemoglobin S polymerization studied by NMR. Res. Biomed. Eng. 38, 831–838 (2022). https://doi.org/10.1007/s42600-022-00224-0

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