SK acknowledges the financial support from DBT, Government of India through extramural projects.
The authors have declared no competing interest. Supplementation of the depleted trace metals and targeting the perturbed metabolic pathways in the RBCs of SCD patients may provide avenues for the development of alternate therapeutics. Interestingly, higher pyroglutamic acid levels were observed in the sickle shaped-RBCs indicating a perturbed gamma-glutamyl pathway in SCD patients. A set of 136 features showed differential (p☑) regulation and was involved in D-glutamine/D-glutamate, sphingolipid, arginine biosynthesis, glutathione and glycine, serine and threonine metabolism. Mass spectrometry analysis of red blood cells (RBCs of SCD (n=5) and healthy controls (n=5) identified 442 unique metabolic features which separately clustered both the study groups in principal component analysis (PCA). These changes in elemental levels, with a decreased Rb/K ratio in the SCD group, may explain the observed frequent hemolysis and severe dehydration with oxidative stress in patients. SCD patients had higher plasma 24Mg, 44Ca, 66Zn, 208Pb, and 39K levels and lower levels of 57Fe, 77Se, and 85Rb compared to controls.
Additionally, comparative global erythrocyte metabolomics of SCD (n=5, male:100%) and healthy controls (n=5, male:100%) were carried out using liquid chromatography-mass spectrometry (LC-MS). In this study, the plasma elemental ( 24Mg, 44Ca, 57Fe, 63Cu, 66Zn, 77Se, 85Rb, 208Pb, and 39K) levels of SCD patients (n=10, male: 50%) and control groups (trait and healthy n=10 each male: 50%) were profiled using inductively coupled plasma mass spectrometry (ICP-MS). Patients suffering from sickle cell disease (SCD) present with multifactorial pathology, and a detailed understanding of it may help to develop novel therapeutics.
0 kommentar(er)
