Effect of hydroxyurea (HU) on gelatinization mechanism of type I collagen suspensions

Abstract

Mutant hemoglobins thermodynamic phase transitions (HbS, HbC, etc.) have been the causes of serious hemoglobinopathies that have been affecting mankind since the dawn of human race. HbS polymerization is the best known of these transitions and the original cause of sickle cell anemia. Hydroxyurea (HU, NH2CONHOH) is widely used as the main drug administered for the treatment of Sickle Cell Anemia (SCA). Several hypotheses have been raised on the effects of HU on SCA. The most widespread and accepted one points to the production of fetal hemoglobin by the bone marrow, hindering the polymerization of deoxygen-ated HbS. Moreover, recent studies have reported that the short term in vivo effects of the HU have not been elucidated. By ordinary techniques of Materials Science (scanning electron microscopy, viscoelasticity, vis-cosity measurements, DSC and weight loss) we assessed the anti-nucleating, depolymerizing, and anti-gelling direct effects of HU on suspensions and type I bovine collagen gels. Scanning electron microscopy (SEM) revealed that the addition of HU results in the disappearance of the percolating three-dimensional network typical of collagen gels. Vane Rheometry tests pointed to a reduction in the yield stress (σ0) by add-ing HU into collagen gels with a concentration of 2.2 % w/v. In the liquid phase (sol), suspensions increased viscosity over time but decreased with the addition of HU, highlighting the depolymerizing effect of this substance. The weight loss of the sols is also affect by the addition of HU probably related to the lowering of the interactions between collagen/water as HU is added. The DSC essays indicated changes in the Cp curves as HU is added to the gel, decreasing the structural relaxations commonly observed in those gels. As a result, HU showed an effect on the phase transition of the studied gel, strengthening the hypothesis of anti-nucleating and anti-gelling action thereof on physical, reversible gels, and possibly on physical, reversible gels of mutant hemoglobin (HbS).
Keywords: hydroxyurea, gelation, collagen, polymerization, sickle cell anemia.