The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age

Williams, Brock A; Cochrane, Kelsey M; Fischer, Jordie A J; Aljaadi, Abeer M.; McAnena, Liadhan; Ward, Mary; McNulty, Helene; Kroeun, Hou; Green, Timothy; Whitfield, Kyly C.; Karakochuk, Crystal D

doi:10.1093/jn/nxaa119

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…Single-nucleotide polymorphisms in riboflavin transporters, which could affect intracellular levels of riboflavin, have been reported, but their association with malaria has not been studied yet [23]. In conclusion, although multiple studies have provided indirect evidence that riboflavin metabolism and levels could be genetically regulated, it is unclear how these regulations are associated with malaria [24][25][26]. Though the mechanistic pathways remain poorly understood, riboflavin has been considered a potential antimalarial target since the 1940s.…”

Section: Is There An Evolutionary Selective Pressure On Riboflavin De...mentioning

confidence: 99%

Role of riboflavin deficiency in malaria pathophysiology

Sharma,

Ramachandran,

Sharma

2024

PLoS Pathog

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The emergence of resistance against antimalarials and insecticides poses a significant threat to malaria elimination strategies. It is crucial to explore potential risk factors for malaria to identify new targets and alternative therapies. Malnutrition is a well-established risk factor for malaria. Deficiencies of micronutrients such as vitamin A, zinc, iron, folic acid, and phenotypic measures of malnutrition, such as stunting and wasting, have been studied extensively in the context of malaria. Vitamin B2, also known as riboflavin, is a micronutrient involved in maintaining cellular homeostasis. Riboflavin deficiency has been shown to have an inverse correlation with malarial parasitaemia. This article reviews the role of riboflavin in maintaining redox homeostasis and probes how riboflavin deficiency could alter malaria pathogenesis by disrupting the balance between oxidants and antioxidants. Though riboflavin analogues have been explored as antimalarials, new in vivo and patient-based research is required to target riboflavin-associated pathways for antimalarial therapy.

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Section: Is There An Evolutionary Selective Pressure On Riboflavin De...mentioning

confidence: 99%

Role of riboflavin deficiency in malaria pathophysiology

Sharma,

Ramachandran,

Sharma

2024

PLoS Pathog

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Riboflavin intake and status and relationship to anemia

2022

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Riboflavin in its coenzyme forms, flavin mononucleotide and flavin adenine dinucleotide, is essential for multiple redox reactions necessary for energy production, antioxidant protection, and metabolism of other B vitamins, such as niacin, pyridoxine, and folate. Erythrocyte glutathione reductase activity coefficient (EGRac) is a biomarker of riboflavin status; ratios ≥1.40 are commonly interpreted as indicating biochemical deficiency. Most research on riboflavin status comes from low-income countries and rural settings, which reported high rates of riboflavin deficiency and inadequate intake. However, some studies suggest that riboflavin deficiency, based on the functional indicator EGRac, is also of concern in middle- and high-income countries. Biochemical riboflavin deficiency that does not cause clinical symptoms may contribute to anemia, particularly among women and children. Riboflavin enhances iron absorption, and riboflavin deficiency decreases iron mobilization from stores. The current knowledge on riboflavin’s role in metabolic processes and its biochemical status is summarized in this review, and the available evidence on the role of riboflavin in anemia among different populations is discussed.

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Riboflavin (Vitamin B2) Deficiency Induces Apoptosis Mediated by Endoplasmic Reticulum Stress and the CHOP Pathway in HepG2 Cells

Zhang

Cao

et al. 2022

Nutrients

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Riboflavin is an essential micronutrient and a precursor of flavin mononucleotide and flavin adenine dinucleotide for maintaining cell homeostasis. Riboflavin deficiency (RD) induces cell apoptosis. Endoplasmic reticulum (ER) stress is considered to induce apoptosis, and C/EBP homologous protein (CHOP) is a key pathway involved in this process. However, whether RD-induced apoptosis is mediated by ER stress and the CHOP pathway remains unclear and needs further investigation. Therefore, the current study presents the effect of RD on ER stress and apoptosis in the human hepatoma cell line (HepG2). Firstly, cells were cultured in a RD medium (4.55 nM riboflavin) and a control (CON) medium (1005 nM riboflavin). We conducted an observation of cell microstructure characterization and determining apoptosis. Subsequently, 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, was used in HepG2 cells to investigate the role of ER stress in RD-induced apoptosis. Finally, CHOP siRNA was transfected into HepG2 cells to validate whether RD triggered ER stress-mediated apoptosis by the CHOP pathway. The results show that RD inhibited cell proliferation and caused ER stress, as well as increased the expression of ER stress markers (CHOP, 78 kDa glucose-regulated protein, activating transcription factor 6) (p < 0.05). Furthermore, RD increased the cell apoptosis rate, enhanced the expression of proapoptotic markers (B-cell lymphoma 2-associated X, Caspase 3), and decreased the expression of the antiapoptotic marker (B-cell lymphoma 2) (p < 0.05). The 4-PBA treatment and CHOP knockdown markedly alleviated RD-induced cell apoptosis. These results demonstrate that RD induces cell apoptosis by triggering ER stress and the CHOP pathway.

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The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age

Abstract: ABSTRACT Background Riboflavin is required for erythropoiesis, which is increased in people with hemoglobinopathies due to increased hemolysis and erythrocyte turnover. Dietary intake and status of riboflavin is poor in Cambodia, where hemoglobinopathies are common. Objective … Show more

Cited by 3 publications

References 46 publications

Role of riboflavin deficiency in malaria pathophysiology

Role of riboflavin deficiency in malaria pathophysiology

Riboflavin intake and status and relationship to anemia

Riboflavin (Vitamin B2) Deficiency Induces Apoptosis Mediated by Endoplasmic Reticulum Stress and the CHOP Pathway in HepG2 Cells

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