Gladys Latunde-dada - Academia.edu (original) (raw)

Papers by Gladys Latunde-dada

Journal of Agricultural and Food Chemistry, 2016

Interest in the consumption of insects (entomophagy) as an alternative environmentally sustainabl... more Interest in the consumption of insects (entomophagy) as an alternative environmentally sustainable source of protein in the diet of humans has recently witnessed a surge. Knowledge of the nutrient composition and, in particular, the bioavailability of minerals from insects is currently sparse. This study evaluated the availability of Fe, Ca, Cu, Mg, Mn, and Zn from four commonly eaten insects and compared these to sirloin beef. Soluble iron from the samples was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Iron bioavailability was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Cricket and sirloin beef had comparably higher levels of Fe, Ca, and Mn than grasshopper, meal, and buffalo worms. However, iron solubility was significantly higher from the insect samples than from beef. The complementation of whole-wheat flour with insect or beef protein resulted in overall decreases in mineral content and iron solubility in the composite mixtures. Collectively, the data show that grasshopper, cricket, and mealworms contain significantly higher chemically available Ca, Cu, Mg, Mn, and Zn than sirloin. However, buffalo worms and sirloin exhibited higher iron bioavailability comparable to that of FeSO4. Commonly consumed insect species could be excellent sources of bioavailable iron and could provide the platform for an alternative strategy for increased mineral intake in the diets of humans.

Medical Hypotheses, 2016

Heme is of significant importance in iron nutrition and in systemic iron metabolism. The crux of ... more Heme is of significant importance in iron nutrition and in systemic iron metabolism. The crux of the matter is that while much is known about non-heme metabolism, the vectorial import of exogenous porphyrin macromolecules into the enterocyte and possibly into blood circulation is still speculative. The inhibitory effect of calcium on heme iron absorption has been previously reported in the literature. This paper postulates that the gastrointestinal Ca transporter, TRPV6, might be a putative transporter of heme and might account for reduced heme absorption in the presence of Ca. The hypothesis needs to be investigated in vitro and in vivo with targeted TRPV6 deletion models to explore the nature of the competitive inhibition of heme uptake by Ca. Studies are required to characterize fully this function in the gut and in systemic metabolism. If the hypothesis is proven, modulators of TRPV6 expression could have clinical implications in the management of heme-induced disorders.

International journal of hematology, Jan 12, 2017

Atonal homolog 8 (ATOH8) is defined as a positive regulator of hepcidin transcription, which link... more Atonal homolog 8 (ATOH8) is defined as a positive regulator of hepcidin transcription, which links erythropoietic activity with iron-sensing molecules. In the present study, we investigated the association between hepcidin and ATOH8 expression in β-thalassemia. We found that inhibition of hepcidin expression in β-thalassemia is correlated with reduced ATOH8 expression. Hepatic hepcidin 1 (Hamp1) and Atoh8 mRNA expression were down-regulated in β-thalassemic mice. Hepcidin (HAMP) and ATOH8 mRNA expression were consistently suppressed in Huh7 cells cultured in medium supplemented with β-thalassemia patient serum. The Huh7 cells, which were transfected with ATOH8-FLAG expression plasmid and cultured in the supplemented medium, exhibited increased levels of ATOH8 mRNA, ATOH8-FLAG protein, pSMAD1,5,8, and HAMP mRNA. Interestingly, over-expression of ATOH8 reversed the effects of hepcidin suppression induced by the β-thalassemia patient sera. In conclusion, hepcidin suppression in β-thala...

Biochimica et biophysica acta, 2017

Ferroptosis is a form of regulated cell death that is dependent on iron and reactive oxygen speci... more Ferroptosis is a form of regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is morphologically and biochemically distinct and disparate from other processes of cell death. As ferroptosis is induced by inhibition of cysteine uptake or inactivation of the lipid repair enzyme glutathione peroxidase 4 (GPX4), the process is favored by chemical or mutational inhibition of the cystine/glutamate antiporter and culminates in the accumulation of reactive oxygen species (ROS) in the form of lipid hydroperoxides. Excessive lipid peroxidation leads to death by ferroptosis and the phenotype is accentuated respectively by the repletion and depletion of iron and glutathione in cells. Furthermore, oxidized phosphatidylethanolamines (PE) harbouring arachidonoyl (AA) and adrenoyl moieties (AdA) have been shown as proximate executioners of ferroptosis. Induction of ferroptosis due to cysteine depletion leads to the degradatio...

British Journal of Nutrition, 2017

Strategies for preventing Fe deficiency include Fe supplementation and Fe fortification of foods.... more Strategies for preventing Fe deficiency include Fe supplementation and Fe fortification of foods. The absorption, metabolism and chemical characteristics of Fe multi-amino acid chelate (IMAAC) are not known. Absorption of IMAAC was compared with FeSO4 in Fe-depleted mice and in vitro chemical studies of the Fe supplement was performed in HuTu 80 cells. Hb repletion study was carried out in Fe-deficient CD1 mice that were fed for 10 d a diet supplemented with ferrous IMAAC or FeSO4. A control group of Fe-replete mice was fed a diet with adequate Fe concentrations throughout the study. Tissues were collected from the mice, and the expression of Fe-related genes was determined by quantitative PCR. Ferric reductase and Fe uptake were evaluated in HuTu 80 cells. Supplementation of the diet with FeSO4 or IMAAC significantly increased Hb levels (P<0·001) in Fe-deficient mice from initial 93·9 (SD 10·8) or 116·2 (SD 9·1) to 191 (SD 0·7) or 200 (SD 0·5) g/l, respectively. Initial and final Hb for the Fe-deficient control group were 87·4 (SD 6·7) and 111 (SD 11·7) g/l, respectively. Furthermore, the liver non-haem Fe of both supplement groups increased significantly (P<0·001). IMAAC was more effective at restoring Fe in the spleen compared with FeSO4 (P<0·005). Gene expression showed the IMAAC supplement absorption is regulated by the body's Fe status as it significantly up-regulated hepcidin (P<0·001) and down-regulated duodenal cytochrome b mRNA (P<0·005), similar to the effects seen with FeSO4. A significant proportion of Fe in IMAAC is reduced by ascorbic acid. Fe absorption in mice and cells was similar for both IMAAC and FeSO4 and both compounds induce and regulate Fe metabolism genes similarly in the maintenance of homeostasis in mice.

Molecular Nutrition & Food Research, 2016

Scope: Iron is an essential nutrient. However, in animal models, excess unabsorbed dietary iron r... more Scope: Iron is an essential nutrient. However, in animal models, excess unabsorbed dietary iron residing within the colonic lumen has been shown to exacerbate inflammatory bowel disease and intestinal cancer. Therefore the aims of this study were to screen a panel of alginates to identify a therapeutic that can chelate this pool of iron and thus be beneficial for intestinal health. Methods and results: Using several in vitro intestinal models it is evident that only one alginate (Manucol LD) of the panel tested was able to inhibit intracellular iron accumulation as assessed by iron mediated ferritin induction, transferrin receptor expression, intracellular (59) Fe concentrations and by measuring iron flux across a Caco-2 monolayer. Additionally, Manucol LD suppressed iron absorption in mice which was associated with increased faecal iron levels indicating iron chelation within the gastrointestinal tract. Furthermore, the bioactivity of Manucol LD was found to be highly dependent on both its molecular weight and its unique compositional sequence. Conclusion: Manucol LD could be useful for the chelation of this detrimental pool of unabsorbed iron and it could be fortified in foods to enhance intestinal health. This article is protected by copyright. All rights reserved.

PLOS ONE, 2015

Alginates are a class of biopolymers with known iron binding properties which are routinely used ... more Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease.

Journal of Functional Foods, 2015

Journal of Nutrition, 2012

Duodenal cytochrome b (Dcytb, Cybrd1) is a ferric reductase localized in the duodenum that is hig... more Duodenal cytochrome b (Dcytb, Cybrd1) is a ferric reductase localized in the duodenum that is highly upregulated in circumstances of increased iron absorption. To address the contribution of Dcytb to total duodenal ferric reductase activity as well as its wider role in iron metabolism, we first measured duodenal ferric reductase activity in wild-type (WT) and

British Journal of Nutrition, 2011

Hepcidin, the Fe-regulatory peptide, has been shown to inhibit Fe absorption and reticuloendothel... more Hepcidin, the Fe-regulatory peptide, has been shown to inhibit Fe absorption and reticuloendothelial Fe recycling. The present study was conducted to explore the mechanism of in vivo Fe regulation through genetic disruption of hepcidin1 and acute effects of hepcidin treatment in hepcidin1 knockout (Hepc1 2/ 2 ) and heterozygous mice. Hepcidin1 disruption resulted in significantly increased intestinal Fe uptake. Hepcidin injection inhibited Fe absorption in both genotypes, but the effects were more evident in the knockout mice. Hepcidin administration was also associated with decreased membrane localisation of ferroportin in the duodenum, liver and, most significantly, in the spleen of Hepc1 2/2 mice. Hypoferraemia was induced in heterozygous mice by hepcidin treatment, but not in Hepc1 2/2 mice, 4 h after injection. Interestingly, Fe absorption and serum Fe levels in Hepc1 2/2 and heterozygous mice fed a low-Fe diet were not affected by hepcidin injection. The present study demonstrates that hepcidin deficiency causes increased Fe absorption. The effects of hepcidin were abolished by dietary Fe deficiency, indicating that the response to hepcidin may be influenced by dietary Fe level or Fe status.

Scandinavian Journal of Immunology, 1992

Iron deficiency is often associated with the impairment of the immune system, particularly the fu... more Iron deficiency is often associated with the impairment of the immune system, particularly the functioning of T-cell lymphocytes. Studies were therefore carried out in mice to investigate the involvement of iron in T-cell functions. Iron deficiency in mice was induced nutritionally by feeding diets differing in iron content for 4 weeks to produce normal, moderately low and severely low haematological indices. The proliferation of lymphocytes stimulated by Con A from these groups of mice was significantly affected by the degree of iron deficiency. Iron depletion also resulted in decreased production of interleukin 2 (IL-2) in the proliferating cells. The implications of these findings in the manifestation of iron deficiency anaemia are discussed.

Nutrition & Metabolism, 2011

Telfairia occidentalis is a vegetable food crop that is indigenous to West Africa. The leaves and... more Telfairia occidentalis is a vegetable food crop that is indigenous to West Africa. The leaves and seeds are the edible parts of the plant and are used in everyday meals by incorporation into soups and stews. Previous studies have attributed improved haematological indices to the vegetable and have advocated the use of T. occidentalis in the treatment of anemia. This study investigates the ameliorative effects of T. occidentalis when compared to FeSO 4 as a reference salt in anaemic mice. It also compares the bioavailability of test iron and hepatic hepcidin expression for the estimation of iron absorption in the mice. Non-haem iron was determined in the liver of mice after the experimental feeding treatments. Hepcidin mRNA expression was carried out by quantitative RT-PCR. Administration of T. occidentalis leaves led to a modest increase in haemoglobin (Hb) levels in anaemic mice that were comparable to the Hb repletion in anaemic mice given FeSO 4. Hepatic iron increase in the mice given either T. occidentalis or FeSO 4 led to a corresponding enhancement of hepcidin mRNA expression. Induced hepcidin mRNA expression was enhanced by the addition of ascorbic acid to the test dose of iron. Hepatic hepcidin mRNA expression was found to be responsive to increase in the relative bioavailability of iron from test diets.

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2002

Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS).... more Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS). The aim of the study was to determine whether physiological ferric/ferrous iron induces oxidative DNA damage in human colon cells. Therefore, differentiated human colon tumour cells (HT29 clone 19A) were incubated with ferric-nitrilotriacetate (Fe-NTA) or with haemoglobin and DNA breaks and oxidised bases were determined by microgelelectrophoresis. The effects of Fe-NTA were measured with additional H 2 O 2 (75 M) and quercetin (25-100 M) treatment. Analytic detection of iron in cell cultures, treated with 250 M Fe-NTA for 15 min to 24 h, showed that 48.02 ± 5.14 to 68.31 ± 2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000 M) induced DNA breaks and oxidised bases, which were enhanced by subsequent H 2 O 2 exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H 2 O 2 for 15 min, 37 • C did not change the effect of H 2 O 2 alone. The impact of Fe-NTA and H 2 O 2 -induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H 2 O 2 -control). Haemoglobin was as effective as Fe-NTA in inducing DNA damage. From these results we can conclude that iron is taken up by human colon cells and participates in the induction of oxidative DNA damage. Thus, iron or its capacity to catalyse ROS-formation, is an important colon cancer risk factor. Inhibition of damage by quercetin reflects the potential of antioxidative compounds to influence this risk factor. Quantitative data on the genotoxic impact of ferrous iron (e.g. from red meat) relative to the concentrations of antioxidants (from plant foods) in the gut are now needed to determine the optimal balance of food intake that will reduce exposure to this type of colon cancer risk factor.

Journal of Biological Chemistry, 2012

The mechanism by which anemia results in lowered hepcidin levels is not clear. Results: Bone morp... more The mechanism by which anemia results in lowered hepcidin levels is not clear. Results: Bone morphogenetic protein (BMP)-binding endothelial cell precursor-derived regulator (BMPER), a known BMP antagonist, was found to be up-regulated in anemic Trf hpx/hpx mice and to suppress hepcidin transcription both in vivo and in vitro. Conclusion: BMPER is involved in suppressing hepcidin levels in Trf hpx/hpx mice. Significance: BMPER is a novel regulator of hepcidin and iron metabolism.

International Journal of Food Sciences and Nutrition, 1993

... Akinyele 10, Onigbinde AO, Hussain MA & Omololu A (1986): Physicochemical characteristics... more ... Akinyele 10, Onigbinde AO, Hussain MA & Omololu A (1986): Physicochemical characteristics of 18 cultivars of Nigerian cowpeas (V. unguiculuta ... Uzogara SG, Morton JD & Daniel JW (1988): Quality changes and mineral content of cowpea (Vigna unguiculata L. Walp) seeds ...

FEBS Letters, 2012

Keywords: Hypoxia Copper uptake Ctr1 Caco-2 cell DMT1 Duodenum a b s t r a c t Hypoxia, via stabi... more Keywords: Hypoxia Copper uptake Ctr1 Caco-2 cell DMT1 Duodenum a b s t r a c t Hypoxia, via stabilization of HIF2a, regulates the expression of the intestinal iron transporters DMT1 and ferroportin. Here we investigated whether the intestinal copper importer Ctr1 was also regulated by hypoxia. Copper uptake and Ctr1 mRNA expression were significantly increased in Caco-2 cells exposed to hypoxia. To determine whether HIF2a was involved in regulation of Ctr1 expression, we employed three models of HIF2a knockdown (chemical suppression of HIF2a translation in Caco-2 cells; HIF2a-siRNA-treated HuTu80 cells; HIF2a-intestinal knockout mice); Ctr1 mRNA expression was decreased in all three models under normoxic conditions. HIF2a translational inhibitor did not alter Ctr1 expression under hypoxic conditions. We conclude that basal expression of Ctr1 is regulated by HIF2a; however, the induction by hypoxia is a HIF2a-independent event.

European Journal of Haematology, 2013

Iron is an important mineral element required for diverse life processes. Its metabolism is almos... more Iron is an important mineral element required for diverse life processes. Its metabolism is almost synonymous to erythrocyte maintenance, erythropoiesis and erythrophagocytosis. Consequently, exercise exertion impacts significantly on red cell haematology. Here, the interactions between exercise and erythropoiesis are explored. Hepcidin, the peptide hormone that regulates systemic iron metabolism, decreases in response to erythropoiesis by facilitating increased iron efflux from ferroportin into circulation. However, during exercise, there is an alarming increase in the expression of hepcidin resulting in a negative iron balance in athletes. In this review, the confounding cause and effect scenarios of exercise, athlete training and haematology and hepcidin interactions are discussed.

British Journal of Haematology, 2014

ATOH8 has previously been shown to be an iron-regulated transcription factor, however its role in... more ATOH8 has previously been shown to be an iron-regulated transcription factor, however its role in iron metabolism is not known. ATOH8 expression in HEK293 cells resulted in increased endogenous HAMP mRNA levels as well as HAMP promoter activity. Mutation of the E-box or SMAD response elements within the HAMP promoter significantly reduced the effects of ATOH8, indicating that ATOH8 activates HAMP transcription directly as well as through bone morphogenic protein (BMP) signalling. In support of the former, Chromatin immunoprecipitation assays provided evidence that ATOH8 binds to E-box regions within the HAMP promoter while the latter was supported by the finding that ATOH8 expression in HEK293 cells led to increased phosphorylated SMAD1,5,8 levels. Liver Atoh8 levels were reduced in mice under conditions associated with increased erythropoietic activity such as hypoxia, haemolytic anaemia, hypotransferrinaemia and erythropoietin treatment and increased by inhibitors of erythropoiesis. Hepatic Atoh8 mRNA levels increased in mice treated with holo transferrin, suggesting that Atoh8 responds to changes in plasma iron. ATOH8 is therefore a novel transcriptional regulator of HAMP, which is responsive to changes in plasma iron and erythroid activity and could explain how changes in erythroid activity lead to regulation of HAMP.

Journal of Agricultural and Food Chemistry, 2016

Interest in the consumption of insects (entomophagy) as an alternative environmentally sustainabl... more Interest in the consumption of insects (entomophagy) as an alternative environmentally sustainable source of protein in the diet of humans has recently witnessed a surge. Knowledge of the nutrient composition and, in particular, the bioavailability of minerals from insects is currently sparse. This study evaluated the availability of Fe, Ca, Cu, Mg, Mn, and Zn from four commonly eaten insects and compared these to sirloin beef. Soluble iron from the samples was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Iron bioavailability was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Cricket and sirloin beef had comparably higher levels of Fe, Ca, and Mn than grasshopper, meal, and buffalo worms. However, iron solubility was significantly higher from the insect samples than from beef. The complementation of whole-wheat flour with insect or beef protein resulted in overall decreases in mineral content and iron solubility in the composite mixtures. Collectively, the data show that grasshopper, cricket, and mealworms contain significantly higher chemically available Ca, Cu, Mg, Mn, and Zn than sirloin. However, buffalo worms and sirloin exhibited higher iron bioavailability comparable to that of FeSO4. Commonly consumed insect species could be excellent sources of bioavailable iron and could provide the platform for an alternative strategy for increased mineral intake in the diets of humans.

Medical Hypotheses, 2016

Heme is of significant importance in iron nutrition and in systemic iron metabolism. The crux of ... more Heme is of significant importance in iron nutrition and in systemic iron metabolism. The crux of the matter is that while much is known about non-heme metabolism, the vectorial import of exogenous porphyrin macromolecules into the enterocyte and possibly into blood circulation is still speculative. The inhibitory effect of calcium on heme iron absorption has been previously reported in the literature. This paper postulates that the gastrointestinal Ca transporter, TRPV6, might be a putative transporter of heme and might account for reduced heme absorption in the presence of Ca. The hypothesis needs to be investigated in vitro and in vivo with targeted TRPV6 deletion models to explore the nature of the competitive inhibition of heme uptake by Ca. Studies are required to characterize fully this function in the gut and in systemic metabolism. If the hypothesis is proven, modulators of TRPV6 expression could have clinical implications in the management of heme-induced disorders.

International journal of hematology, Jan 12, 2017

Atonal homolog 8 (ATOH8) is defined as a positive regulator of hepcidin transcription, which link... more Atonal homolog 8 (ATOH8) is defined as a positive regulator of hepcidin transcription, which links erythropoietic activity with iron-sensing molecules. In the present study, we investigated the association between hepcidin and ATOH8 expression in β-thalassemia. We found that inhibition of hepcidin expression in β-thalassemia is correlated with reduced ATOH8 expression. Hepatic hepcidin 1 (Hamp1) and Atoh8 mRNA expression were down-regulated in β-thalassemic mice. Hepcidin (HAMP) and ATOH8 mRNA expression were consistently suppressed in Huh7 cells cultured in medium supplemented with β-thalassemia patient serum. The Huh7 cells, which were transfected with ATOH8-FLAG expression plasmid and cultured in the supplemented medium, exhibited increased levels of ATOH8 mRNA, ATOH8-FLAG protein, pSMAD1,5,8, and HAMP mRNA. Interestingly, over-expression of ATOH8 reversed the effects of hepcidin suppression induced by the β-thalassemia patient sera. In conclusion, hepcidin suppression in β-thala...

Biochimica et biophysica acta, 2017

Ferroptosis is a form of regulated cell death that is dependent on iron and reactive oxygen speci... more Ferroptosis is a form of regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is morphologically and biochemically distinct and disparate from other processes of cell death. As ferroptosis is induced by inhibition of cysteine uptake or inactivation of the lipid repair enzyme glutathione peroxidase 4 (GPX4), the process is favored by chemical or mutational inhibition of the cystine/glutamate antiporter and culminates in the accumulation of reactive oxygen species (ROS) in the form of lipid hydroperoxides. Excessive lipid peroxidation leads to death by ferroptosis and the phenotype is accentuated respectively by the repletion and depletion of iron and glutathione in cells. Furthermore, oxidized phosphatidylethanolamines (PE) harbouring arachidonoyl (AA) and adrenoyl moieties (AdA) have been shown as proximate executioners of ferroptosis. Induction of ferroptosis due to cysteine depletion leads to the degradatio...

British Journal of Nutrition, 2017

Strategies for preventing Fe deficiency include Fe supplementation and Fe fortification of foods.... more Strategies for preventing Fe deficiency include Fe supplementation and Fe fortification of foods. The absorption, metabolism and chemical characteristics of Fe multi-amino acid chelate (IMAAC) are not known. Absorption of IMAAC was compared with FeSO4 in Fe-depleted mice and in vitro chemical studies of the Fe supplement was performed in HuTu 80 cells. Hb repletion study was carried out in Fe-deficient CD1 mice that were fed for 10 d a diet supplemented with ferrous IMAAC or FeSO4. A control group of Fe-replete mice was fed a diet with adequate Fe concentrations throughout the study. Tissues were collected from the mice, and the expression of Fe-related genes was determined by quantitative PCR. Ferric reductase and Fe uptake were evaluated in HuTu 80 cells. Supplementation of the diet with FeSO4 or IMAAC significantly increased Hb levels (P<0·001) in Fe-deficient mice from initial 93·9 (SD 10·8) or 116·2 (SD 9·1) to 191 (SD 0·7) or 200 (SD 0·5) g/l, respectively. Initial and final Hb for the Fe-deficient control group were 87·4 (SD 6·7) and 111 (SD 11·7) g/l, respectively. Furthermore, the liver non-haem Fe of both supplement groups increased significantly (P<0·001). IMAAC was more effective at restoring Fe in the spleen compared with FeSO4 (P<0·005). Gene expression showed the IMAAC supplement absorption is regulated by the body's Fe status as it significantly up-regulated hepcidin (P<0·001) and down-regulated duodenal cytochrome b mRNA (P<0·005), similar to the effects seen with FeSO4. A significant proportion of Fe in IMAAC is reduced by ascorbic acid. Fe absorption in mice and cells was similar for both IMAAC and FeSO4 and both compounds induce and regulate Fe metabolism genes similarly in the maintenance of homeostasis in mice.

Molecular Nutrition & Food Research, 2016

Scope: Iron is an essential nutrient. However, in animal models, excess unabsorbed dietary iron r... more Scope: Iron is an essential nutrient. However, in animal models, excess unabsorbed dietary iron residing within the colonic lumen has been shown to exacerbate inflammatory bowel disease and intestinal cancer. Therefore the aims of this study were to screen a panel of alginates to identify a therapeutic that can chelate this pool of iron and thus be beneficial for intestinal health. Methods and results: Using several in vitro intestinal models it is evident that only one alginate (Manucol LD) of the panel tested was able to inhibit intracellular iron accumulation as assessed by iron mediated ferritin induction, transferrin receptor expression, intracellular (59) Fe concentrations and by measuring iron flux across a Caco-2 monolayer. Additionally, Manucol LD suppressed iron absorption in mice which was associated with increased faecal iron levels indicating iron chelation within the gastrointestinal tract. Furthermore, the bioactivity of Manucol LD was found to be highly dependent on both its molecular weight and its unique compositional sequence. Conclusion: Manucol LD could be useful for the chelation of this detrimental pool of unabsorbed iron and it could be fortified in foods to enhance intestinal health. This article is protected by copyright. All rights reserved.

PLOS ONE, 2015

Alginates are a class of biopolymers with known iron binding properties which are routinely used ... more Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease.

Journal of Functional Foods, 2015

Journal of Nutrition, 2012

Duodenal cytochrome b (Dcytb, Cybrd1) is a ferric reductase localized in the duodenum that is hig... more Duodenal cytochrome b (Dcytb, Cybrd1) is a ferric reductase localized in the duodenum that is highly upregulated in circumstances of increased iron absorption. To address the contribution of Dcytb to total duodenal ferric reductase activity as well as its wider role in iron metabolism, we first measured duodenal ferric reductase activity in wild-type (WT) and

British Journal of Nutrition, 2011

Hepcidin, the Fe-regulatory peptide, has been shown to inhibit Fe absorption and reticuloendothel... more Hepcidin, the Fe-regulatory peptide, has been shown to inhibit Fe absorption and reticuloendothelial Fe recycling. The present study was conducted to explore the mechanism of in vivo Fe regulation through genetic disruption of hepcidin1 and acute effects of hepcidin treatment in hepcidin1 knockout (Hepc1 2/ 2 ) and heterozygous mice. Hepcidin1 disruption resulted in significantly increased intestinal Fe uptake. Hepcidin injection inhibited Fe absorption in both genotypes, but the effects were more evident in the knockout mice. Hepcidin administration was also associated with decreased membrane localisation of ferroportin in the duodenum, liver and, most significantly, in the spleen of Hepc1 2/2 mice. Hypoferraemia was induced in heterozygous mice by hepcidin treatment, but not in Hepc1 2/2 mice, 4 h after injection. Interestingly, Fe absorption and serum Fe levels in Hepc1 2/2 and heterozygous mice fed a low-Fe diet were not affected by hepcidin injection. The present study demonstrates that hepcidin deficiency causes increased Fe absorption. The effects of hepcidin were abolished by dietary Fe deficiency, indicating that the response to hepcidin may be influenced by dietary Fe level or Fe status.

Scandinavian Journal of Immunology, 1992

Iron deficiency is often associated with the impairment of the immune system, particularly the fu... more Iron deficiency is often associated with the impairment of the immune system, particularly the functioning of T-cell lymphocytes. Studies were therefore carried out in mice to investigate the involvement of iron in T-cell functions. Iron deficiency in mice was induced nutritionally by feeding diets differing in iron content for 4 weeks to produce normal, moderately low and severely low haematological indices. The proliferation of lymphocytes stimulated by Con A from these groups of mice was significantly affected by the degree of iron deficiency. Iron depletion also resulted in decreased production of interleukin 2 (IL-2) in the proliferating cells. The implications of these findings in the manifestation of iron deficiency anaemia are discussed.

Nutrition & Metabolism, 2011

Telfairia occidentalis is a vegetable food crop that is indigenous to West Africa. The leaves and... more Telfairia occidentalis is a vegetable food crop that is indigenous to West Africa. The leaves and seeds are the edible parts of the plant and are used in everyday meals by incorporation into soups and stews. Previous studies have attributed improved haematological indices to the vegetable and have advocated the use of T. occidentalis in the treatment of anemia. This study investigates the ameliorative effects of T. occidentalis when compared to FeSO 4 as a reference salt in anaemic mice. It also compares the bioavailability of test iron and hepatic hepcidin expression for the estimation of iron absorption in the mice. Non-haem iron was determined in the liver of mice after the experimental feeding treatments. Hepcidin mRNA expression was carried out by quantitative RT-PCR. Administration of T. occidentalis leaves led to a modest increase in haemoglobin (Hb) levels in anaemic mice that were comparable to the Hb repletion in anaemic mice given FeSO 4. Hepatic iron increase in the mice given either T. occidentalis or FeSO 4 led to a corresponding enhancement of hepcidin mRNA expression. Induced hepcidin mRNA expression was enhanced by the addition of ascorbic acid to the test dose of iron. Hepatic hepcidin mRNA expression was found to be responsive to increase in the relative bioavailability of iron from test diets.

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2002

Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS).... more Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS). The aim of the study was to determine whether physiological ferric/ferrous iron induces oxidative DNA damage in human colon cells. Therefore, differentiated human colon tumour cells (HT29 clone 19A) were incubated with ferric-nitrilotriacetate (Fe-NTA) or with haemoglobin and DNA breaks and oxidised bases were determined by microgelelectrophoresis. The effects of Fe-NTA were measured with additional H 2 O 2 (75 M) and quercetin (25-100 M) treatment. Analytic detection of iron in cell cultures, treated with 250 M Fe-NTA for 15 min to 24 h, showed that 48.02 ± 5.14 to 68.31 ± 2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000 M) induced DNA breaks and oxidised bases, which were enhanced by subsequent H 2 O 2 exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H 2 O 2 for 15 min, 37 • C did not change the effect of H 2 O 2 alone. The impact of Fe-NTA and H 2 O 2 -induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H 2 O 2 -control). Haemoglobin was as effective as Fe-NTA in inducing DNA damage. From these results we can conclude that iron is taken up by human colon cells and participates in the induction of oxidative DNA damage. Thus, iron or its capacity to catalyse ROS-formation, is an important colon cancer risk factor. Inhibition of damage by quercetin reflects the potential of antioxidative compounds to influence this risk factor. Quantitative data on the genotoxic impact of ferrous iron (e.g. from red meat) relative to the concentrations of antioxidants (from plant foods) in the gut are now needed to determine the optimal balance of food intake that will reduce exposure to this type of colon cancer risk factor.

Journal of Biological Chemistry, 2012

The mechanism by which anemia results in lowered hepcidin levels is not clear. Results: Bone morp... more The mechanism by which anemia results in lowered hepcidin levels is not clear. Results: Bone morphogenetic protein (BMP)-binding endothelial cell precursor-derived regulator (BMPER), a known BMP antagonist, was found to be up-regulated in anemic Trf hpx/hpx mice and to suppress hepcidin transcription both in vivo and in vitro. Conclusion: BMPER is involved in suppressing hepcidin levels in Trf hpx/hpx mice. Significance: BMPER is a novel regulator of hepcidin and iron metabolism.

International Journal of Food Sciences and Nutrition, 1993

... Akinyele 10, Onigbinde AO, Hussain MA & Omololu A (1986): Physicochemical characteristics... more ... Akinyele 10, Onigbinde AO, Hussain MA & Omololu A (1986): Physicochemical characteristics of 18 cultivars of Nigerian cowpeas (V. unguiculuta ... Uzogara SG, Morton JD & Daniel JW (1988): Quality changes and mineral content of cowpea (Vigna unguiculata L. Walp) seeds ...

FEBS Letters, 2012

Keywords: Hypoxia Copper uptake Ctr1 Caco-2 cell DMT1 Duodenum a b s t r a c t Hypoxia, via stabi... more Keywords: Hypoxia Copper uptake Ctr1 Caco-2 cell DMT1 Duodenum a b s t r a c t Hypoxia, via stabilization of HIF2a, regulates the expression of the intestinal iron transporters DMT1 and ferroportin. Here we investigated whether the intestinal copper importer Ctr1 was also regulated by hypoxia. Copper uptake and Ctr1 mRNA expression were significantly increased in Caco-2 cells exposed to hypoxia. To determine whether HIF2a was involved in regulation of Ctr1 expression, we employed three models of HIF2a knockdown (chemical suppression of HIF2a translation in Caco-2 cells; HIF2a-siRNA-treated HuTu80 cells; HIF2a-intestinal knockout mice); Ctr1 mRNA expression was decreased in all three models under normoxic conditions. HIF2a translational inhibitor did not alter Ctr1 expression under hypoxic conditions. We conclude that basal expression of Ctr1 is regulated by HIF2a; however, the induction by hypoxia is a HIF2a-independent event.

European Journal of Haematology, 2013

Iron is an important mineral element required for diverse life processes. Its metabolism is almos... more Iron is an important mineral element required for diverse life processes. Its metabolism is almost synonymous to erythrocyte maintenance, erythropoiesis and erythrophagocytosis. Consequently, exercise exertion impacts significantly on red cell haematology. Here, the interactions between exercise and erythropoiesis are explored. Hepcidin, the peptide hormone that regulates systemic iron metabolism, decreases in response to erythropoiesis by facilitating increased iron efflux from ferroportin into circulation. However, during exercise, there is an alarming increase in the expression of hepcidin resulting in a negative iron balance in athletes. In this review, the confounding cause and effect scenarios of exercise, athlete training and haematology and hepcidin interactions are discussed.

British Journal of Haematology, 2014

ATOH8 has previously been shown to be an iron-regulated transcription factor, however its role in... more ATOH8 has previously been shown to be an iron-regulated transcription factor, however its role in iron metabolism is not known. ATOH8 expression in HEK293 cells resulted in increased endogenous HAMP mRNA levels as well as HAMP promoter activity. Mutation of the E-box or SMAD response elements within the HAMP promoter significantly reduced the effects of ATOH8, indicating that ATOH8 activates HAMP transcription directly as well as through bone morphogenic protein (BMP) signalling. In support of the former, Chromatin immunoprecipitation assays provided evidence that ATOH8 binds to E-box regions within the HAMP promoter while the latter was supported by the finding that ATOH8 expression in HEK293 cells led to increased phosphorylated SMAD1,5,8 levels. Liver Atoh8 levels were reduced in mice under conditions associated with increased erythropoietic activity such as hypoxia, haemolytic anaemia, hypotransferrinaemia and erythropoietin treatment and increased by inhibitors of erythropoiesis. Hepatic Atoh8 mRNA levels increased in mice treated with holo transferrin, suggesting that Atoh8 responds to changes in plasma iron. ATOH8 is therefore a novel transcriptional regulator of HAMP, which is responsive to changes in plasma iron and erythroid activity and could explain how changes in erythroid activity lead to regulation of HAMP.