High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats

Ha, Jung‐Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen; Collins, James F.

doi:10.1371/journal.pone.0161033

Cited by 39 publications

(52 citation statements)

References 49 publications

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“…Our results showed that rats receiving the low-iron diet for 14 days reached a hemoglobin concentration of 5.0 g/dL, and also had a significantly lower body weight (p < 0.05) than the normal rats (87.0 g vs 101.9 g). These observations are consistent with the report by Ha et al [17], confirming that the rats receiving the low-iron diet achieved iron-deficiency anemia after the acclimation period.…”

Section: Acclimation and Iron-deficiency Anemiasupporting

confidence: 93%

“…. As in the study by Ha et al [17], anemic rats remaining on the low-iron diet during the feeding trial gained weight at a slower rate (smaller weekly percent increases) compared to normal rats on the regular diet. However, anemic rats switched to the regular diet were able to gain weight essentially at the same rate as normal rats with or without FOS (Figure 1).…”

Section: Weight Gain and Water Intakementioning

confidence: 60%

“…After 14 days of acclimation, rats receiving the low-iron diet showed lower hemoglobin concentration, as well as lower tissue non-heme iron levels in liver, spleen, kidney and heart, when compared to normal rats (Table 2). In a recent study on iron-copper interactions, Ha et al [17] reported that feeding male Sprague-Dawley rats a diet containing about 12 μg Fe/g diet for 5…”

Section: Acclimation and Iron-deficiency Anemiamentioning

confidence: 99%

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Supplementation of Fructooligosaccharide Mildly Improves the Iron Status of Anemic Rats Fed a Low-Iron Diet

Zhang¹,

Yung²,

Chung³

et al. 2017

FNS

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Also known as a prebiotic, fructooligosaccharide (FOS) resists digestion by gastric acid and pancreatic enzymes in vivo, but is preferentially fermented by beneficial intestinal bacteria once it reaches the colon. While some studies suggest that FOS and its fermentation products may influence the iron absorption process, the effects of prolonged FOS supplementation on iron status remain unclear. The objective of this study was therefore to determine the enhancing effects of FOS supplementation on the iron status of anemic rats. Male Sprague-Dawley rats receiving a low-iron diet (12 μg/g) for 14 days showed significantly lower hemoglobin concentration, as well as lower tissue non-heme iron levels than rats receiving a regular diet (45 μg/g), confirming iron-deficiency anemia. On the first day of the feeding trial, two groups of anemic rats (n = 6) were fed the same low-iron diet with or without FOS supplementation, while two other groups of anemic rats were switched to the regular diet with or without FOS supplementation to allow recovery. FOS was provided to the rats by dissolving in water at 5% (w/v). Anemic rats fed the low-iron diet showed a mild increase (p < 0.05) in hemoglobin level after 21 days of FOS supplementation when compared to rats without FOS. For anemic rats switched to the regular diet, hemoglobin level returned to normal after 14 days and FOS supplementation showed no additional effects. Our results suggest that FOS supplementation has a mild enhancing effect on the iron status of anemic subjects on a low-iron diet.

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Section: Acclimation and Iron-deficiency Anemiasupporting

confidence: 93%

Section: Weight Gain and Water Intakementioning

confidence: 60%

Section: Acclimation and Iron-deficiency Anemiamentioning

confidence: 99%

See 1 more Smart Citation

Supplementation of Fructooligosaccharide Mildly Improves the Iron Status of Anemic Rats Fed a Low-Iron Diet

Zhang¹,

Yung²,

Chung³

et al. 2017

FNS

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show abstract

“…For example, immunoreactive CP was reported to be decreased in hereditary hemochromatosis (HH), a genetic iron-loading disorder (67). Additional recent investigations in rats (112) and mice (110) demonstrated that high-iron intake can lead to copper depletion. In these studies, high-iron fed rodents developed severe copper deficiency-related pathologies, including growth retardation, cardiac hypertrophy, anemia, and impaired production of the liver-derived circulating FOX CP, which is a biomarker of moderate to severe copper deficiency (110, 112).…”

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 98%

“…Additional recent investigations in rats (112) and mice (110) demonstrated that high-iron intake can lead to copper depletion. In these studies, high-iron fed rodents developed severe copper deficiency-related pathologies, including growth retardation, cardiac hypertrophy, anemia, and impaired production of the liver-derived circulating FOX CP, which is a biomarker of moderate to severe copper deficiency (110, 112). Increasing dietary Cu prevented the development of these pathologies in rats, proving that copper deficiency was the underlying cause (112).…”

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 98%

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Doguer

Collins

2018

Comprehensive Physiology

Self Cite

121

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Iron and copper have similar physiochemical properties; thus, physiologically relevant interactions seem likely. Indeed, points of intersection between these two essential trace minerals have been recognized for many decades, but mechanistic details have been lacking. Investigations in recent years have revealed that copper may positively influence iron homeostasis, and also that iron may antagonize copper metabolism. For example, when body iron stores are low, copper is apparently redistributed to tissues important for regulating iron balance, including enterocytes of upper small bowel, the liver, and blood. Copper in enterocytes may positively influence iron transport, and hepatic copper may enhance biosynthesis of a circulating ferroxidase, ceruloplasmin, which potentiates iron release from stores. Moreover, many intestinal genes related to iron absorption are transactivated by a hypoxia-inducible transcription factor, hypoxia-inducible factor-2α (HIF2α), during iron deficiency. Interestingly, copper influences the DNA-binding activity of the HIF factors, thus further exemplifying how copper may modulate intestinal iron homeostasis. Copper may also alter the activity of the iron-regulatory hormone hepcidin. Furthermore, copper depletion has been noted in iron-loading disorders, such as hereditary hemochromatosis. Copper depletion may also be caused by high-dose iron supplementation, raising concerns particularly in pregnancy when iron supplementation is widely recommended. This review will cover the basic physiology of intestinal iron and copper absorption as well as the metabolism of these minerals in the liver. Also considered in detail will be current experimental work in this field, with a focus on molecular aspects of intestinal and hepatic iron-copper interplay and how this relates to various disease states. © 2018 American Physiological Society. Compr Physiol 8:1433-1461, 2018.

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Bioaccessibility and total content of iron, zinc, copper, and manganese in rice varieties (Oryza sativa L.): A probabilistic assessment to evaluate their contribution to dietary reference intake

Ortiz

Cámara-Martos

2018

Cereal Chem

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Background and objectives: Fe, Zn, Cu, and Mn contents as well as bioaccessible fractions of eight rice varieties were analyzed in order to evaluate them nutritionally. Findings: Total trace element concentrations ranged between 5.90 and 15.3 mg/ kg for Fe, 8.82-12.9 mg/kg for Zn, 1.45-5.59 mg/kg for Cu, and 2.45-13.6 mg/ kg for Mn. Brown rice presented the highest trace element contents and at the same time the lowest bioaccessibility. A negative significant statistical correlation was found between dietary fiber and Mn bioaccessibility (r = −0.872; p < 0.01).Significant statistical negative correlations were found between vegetable proteins of rice and trace elements bioaccessibility. Conclusions: A probabilistic assessment (@Risk) used to determine the contribution of DRI for Fe, Zn, Mn, and Cu through the intake of 150-200 g of boiled rice showed that this food can be a proper source of Cu and to a lesser extent Mn but not in the case of Fe and Zn. Significance and novelty: The present study develops a probabilistic model to evaluate the contributions to the DRIs of these micronutrients, from data of rice varieties consumption and their bioaccessibility-total content.

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High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats

Cited by 39 publications

References 49 publications

Supplementation of Fructooligosaccharide Mildly Improves the Iron Status of Anemic Rats Fed a Low-Iron Diet

Supplementation of Fructooligosaccharide Mildly Improves the Iron Status of Anemic Rats Fed a Low-Iron Diet

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Bioaccessibility and total content of iron, zinc, copper, and manganese in rice varieties (Oryza sativa L.): A probabilistic assessment to evaluate their contribution to dietary reference intake

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