Reflection of treatment proficiency of hydroxyurea treated β-thalassemia serum samples through nuclear magnetic resonance based metabonomics

Abstract

β-Thalassemia is a widespread autosomal recessive blood disorder found in most parts of the world. Fetal hemoglobin (HbF), a form of hemoglobin is found in infants, replaced by adult hemoglobin (HbA) after birth. Hydroxyurea (HU) is one of the most effective HbF inducer used for the treatment of anemic diseases. We aimed to improve the understanding of HU therapy in β-thalassemia by metabonomics approach using 1H NMR spectroscopy. This study includes 40 cases of β-thalassemia before and after HU therapy along with 40 healthy as controls. Carr-Purcell-Meiboom-Gill (CPMG) sequence was used to identify forty-one putative metabolites. Generation of models like partial least square discriminant analysis (PLS-DA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) based on different metabolites including lipids, amino acids, glucose, fucose, isobutyrate, and glycerol revealed satisfactory outcomes with 85.2% and 91.1% classification rates, respectively. The concentration of these metabolites was altered in β-thalassemia samples. However, after HU treatment metabolic profile of same patients showed closeness towards healthy. Deviant metabolic pathways counting lipoprotein changes, glycolysis, TCA cycle, fatty acid and choline metabolisms were identified as having significant differences among study groups. Findings of this study may open a better way to monitor HU treatment effectiveness in β-thalassemia patients, as the results suggested that metabolic profile of β-thalassemia patients shows similarity towards normal profile after this therapy.

Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria

“…Moreover, HYD and DFMO have been documented to be useful in chemotherapy for anemia, and sleeping sickness in humans [16,22] and the present study showed their efficacy against mice infected with B. microti, and thus, they might be used as an alternative chemotherapy for humans infected with B. microti after some clinical studies. However, PCR assay should be used alongside optical microscopy in future similar works to detect parasites DNA from in vitro cultures as well as from peripheral blood of animal models in vivo to ensure a total clearance of parasites.…”

“…Cokic et al [15] documented that HYD is well absorbed in vivo, converted to free radical nitroxide and transferred to the cells, whereas the tyrosyl free radical suppression happens at ribonucleotide reductase active site, thereby inhibiting the enzyme. Moreover, HYD has been documented as the best choice for anemic disease treatment such as β-thalassemia [16]. HYD reportedly possesses an antiparasitic activity through blocking Toxoplasma gondii tachyzoite replication [17] and synchronizing the kinetoplast DNA of several parasites, such as Crithidia fasciculate, Leishmania major, L. infantum, L. tarentolae, Trypanosoma brucei, and T. cruzi [16,18].…”

“…Moreover, HYD has been documented as the best choice for anemic disease treatment such as β-thalassemia [16]. HYD reportedly possesses an antiparasitic activity through blocking Toxoplasma gondii tachyzoite replication [17] and synchronizing the kinetoplast DNA of several parasites, such as Crithidia fasciculate, Leishmania major, L. infantum, L. tarentolae, Trypanosoma brucei, and T. cruzi [16,18].…”

Pharmacometabolomics by NMR in Oncology: A Systematic Review

“…Although normalization details were not specified in all the studies, the normalization strategy was mainly dependent on the sample type. Overall, serum and plasma NMR data were preferentially normalized to total area [ 40 , 41 , 46 , 47 , 49 , 51 , 52 , 60 , 67 , 68 , 69 , 71 , 72 , 73 , 74 , 75 , 76 ], although probabilistic quotient normalization [ 26 , 48 , 77 ] and other normalization procedures, such as glucose [ 78 ] or internal standard normalization [ 39 ], were applied in some studies. For urine normalization, total area [ 42 , 67 ] and creatinine signal were the methods most frequently used [ 44 , 79 , 80 ].…”

Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients

“…Before the onset of clinically detectable symptoms, alterations in serum metabolites offers a potential diagnostic biomarker for disease status and predicting response to treatment [15][16][17]. While previous studies identified lipid metabolism as being impacted by the disease and its treatment, the coverage of lipids was limited, mostly to fatty acids.…”