Functional foods: promising therapeutics for Nigerian Children with sickle cell diseases

Abstract

Sickle cell disease (SCD), also known as sickle cell anemia (SCA) is one of the structural hemoglobinopathies that occurs due to a single nucleotide mutation from GAG to GTG, which changes the amino acid of a β-globin chain of hemoglobin (Hb) from glutamate to valine. This singular mutation results to disorderliness in red blood cells (RBCs) with advent of changes in RBC morphology and other pathological conditions. In the 1980s, intermittent red blood cell transfusions, opioids, and penicillin prophylaxis were the only available therapy for SCA and were commonly reserved for acute, life threatening complications. So far, the US Food and Drug Administration (FDA) has granted a total of four drugs approval for the prophylaxis and treatment of the clinical complications of SCD. Due to limitations (adherence, safety, adverse effects) of existing therapies in the prophylaxis and treatment of SCD complications in Nigerian children and their inaccessibility to approved drugs, the present study discusses the therapeutic effects of readily available functional food as one of the therapies or an adjunct therapy to tackle the sickle cell crisis in Nigerian Children.

Keywords: Functional foods; Pediatric/children; Sickle cell disease (SCD).

Figure 1

Schematic of RBC sickling in the vasculature: (a) point mutation from GAG to GTG cause a normal adult hemoglobin HbA to become sickle HbS (b) OxyHbS takes a sickle or banana shape after deoxygenation and polymerizes to form (3) HbS fiber, leading to vaso-occlusion. However, some HbS molecules, with the sickle shape (DeoxyHbS) manage to escape polymerization and undergo reoxygenation and revert back to OxyHbS (desickling). Multiple cycles of sickling and desickling predisposes HbS molecules to hemolysis leading to hemolytic anemia [1, 26].

Figure 2

Pathophysiology of sickle cell disease. Adapted from [24].

Figure 3

HU Mechanism of Action via the Epigenetic and Post Transcriptional Modification: HU inhibits ribonucleotide reductase, the enzyme that converts ribonucleosides (NDP) into deoxyribonucleosides (dNDP). dNDP is required for the synthesis and repair of DNA. Therefore, the inhibition of this enzyme impedes the progression of cellular division (DNA synthesis) through the S-phase, thereby altering erythroid kinetics and causing a reversal via a recovery phase of hematopoietic precursors. This indirect remodeling enhances the recruitment of early erythroid progenitors (such as stress erythropoiesis), which silence the epigenetic signals/enzymes and induce Y-globin expression. HU can also remodel Y-globin gene loci by directly repressing the epigenetic enzymes. DNA methyltransferase 1 (DNMT1); various histone deacetylases (HDAC), lysine demethylase 1 (LSD1, KDM1A); chromodomain helicase DNA binding protein 4 (CHD4); SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5); DNA-binding factors DRED (TR2/TR4); BCL11A: B-cell CLL/lymphoma 11A (BCL11A); Hemoglobin subunit gamma-1 & 2 (HBG1/HBG2) Adapted from [56].

Figure 4

Hu Mechanism of Action Via the Signaling Pathway: NO: nitric oxide; sGC: soluble guanylyl cyclase; GTP: guanosine triphosphate; cGMP: cyclic guanosine monophosphate; p38 MAPK: p38 mitogen-activated protein kinase; SOX6: SRY-Box Transcription Factor 6; LF1: Kruppel Like Factor 1; T-ALL: T-cell acute lymphoblastic; BCL11A: B-cell CLL/lymphoma 11A. Adapted from [57].

Figure 5

Proposed Mechanism of Action for L-glutamine:GA: glutamine aminohydrolase; aKG: A-ketoglutarate; NADS: nicotinamide adenine dinucleotide synthase; G6P: Glucose 6-phosphate; G6PD: Glucose 6-phosphate dehydrogenase; Enzyme 1; Y-glutamyl cysteine synthetase; Enzyme 2: glutathione synthetase; 6-PGL: 6-Phosphogluconolactone; GSH: Reduced Glutathione; GSSH: Oxidized Glutathione. Adapted from [65].

Figure 6

Mechanism of action of Crizanlizumab. P-selectin is predominantly expressed on the endothelial cells and platelets. Adapted from [https://www.creativebiolabs.net].

Figure 7

Graphical summary of actions of some functional foods.

Figure 8

Pictures of Functional Foods: (a) Black beans (Phaseolus vulgaris L); (b) Kiwi (Actinidia deliciosa); (c) Bitter kola (Garania kola H.): (d) Broccoli (Brassica oleracea); (e) Aged garlic (Allium sativum); (f) Walnuts seeds (Juglans regia); (g) Flax seeds (Linum usitatissimum) (h) Chia seed (Salvia hispanica). (Listed functional foods were purchased from local market in Borg El Arab, Egypt).