Influence of nutritional iron deficiency development on some aspects of iron, copper and zinc metabolism

Rodríguez-Matas, M.C.; Lisbona, F.; Gómez-Ayala, A.E.; López-Áliaga, Inmaculada; Campos, Mercedes

doi:10.1258/002367798780559248

Cited by 18 publications

(9 citation statements)

References 24 publications

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“…Our data indicate that maternal Fe deficiency causes deficiency in the fetus, but to a lesser extent than in the mother. These data are in keeping with previous studies showing that available dietary Fe is di- rected toward the formation of new structures and the maintenance of body weight rather than toward Fe stores [39]. In particular, during pregnancy, the fetus has priority for dietary Fe over maternal stores [40], with more than 70% of dietary Fe being delivered to the fetus toward the end of gestation [41].…”

Section: Discussionsupporting

confidence: 90%

Effect of Iron Deficiency on Placental Cytokine Expression and Fetal Growth in the Pregnant Rat1

Gambling¹,

Charania²,

Hannah³

et al. 2002

Biology of Reproduction

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Iron deficiency anemia is the most common nutritional disorder in the world. Anemia is especially serious during pregnancy, with deleterious consequences for both the mother and her developing fetus. We have developed a model to investigate the mechanisms whereby fetal growth and development are affected by maternal anemia. Weanling rats were fed a control or iron-deficient diet before and throughout pregnancy and were killed at Day 21. Dams on the deficient diet had lower hematocrits, serum iron concentrations, and liver iron levels. Similar results were recorded in the fetus, except that the degree of deficiency was markedly less, indicating compensation by the placenta. No effect was observed on maternal weight or the number and viability of fetuses. The fetuses from iron-deficient dams, however, were smaller than controls, with higher placental:fetal ratios and relatively smaller livers. Iron deficiency increased levels of tumor necrosis factor alpha (TNFalpha) only in the trophoblast giant cells of the placenta. In contrast, levels of type 1 TNFalpha receptor increased significantly in giant cells, labyrinth, cytotrophoblast, and fetal vessels. Leptin levels increased significantly in labyrinth and marginally (P = 0.054) in trophoblast giant cells. No change was observed in leptin receptor levels in any region of the placentas from iron-deficient dams. The data show that iron deficiency not only has direct effects on iron levels and metabolism but also on other regulators of growth and development, such as placental cytokines, and that these changes may, in part at least, explain the deleterious consequences of maternal iron deficiency during pregnancy.

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Section: Discussionsupporting

confidence: 90%

Effect of Iron Deficiency on Placental Cytokine Expression and Fetal Growth in the Pregnant Rat1

Gambling¹,

Charania²,

Hannah³

et al. 2002

Biology of Reproduction

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“…ATP7a induction was seen at all ages, and results were similar to those seen for other iron-responsive genes such as DMT1 and Dcytb, which showed not only strong induction but also very high expression levels (Tables 1 and 2). Furthermore, we detected an approximately four to fivefold increase in liver copper levels in 7-to 12-wk-old iron-deficient rats (data not shown), and previous observations have also shown increased body copper levels in iron-deficient rats (32,36) and humans (9). The current study thus provides intriguing evidence that may explain copper loading in the iron-deficient state.…”

Section: Discussionsupporting

confidence: 78%

Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum

Collins

Franck

Kowdley

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

121

123

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We sought to identify novel genes involved in intestinal iron absorption by inducing iron deficiency in rats during postnatal development from the suckling period through adulthood. We then performed comparative gene chip analyses (RAE230A and RAE230B chips; Affymetrix) with cRNA derived from duodenal mucosa. Real-time PCR was used to confirm changes in gene expression. Genes encoding the apical iron transport-related proteins [divalent metal transporter 1 (DMT1) and duodenal cytochrome b] were strongly induced at all ages studied, whereas increases in mRNA encoding the basolateral proteins iron-regulated gene 1 and hephaestin were observed only by real-time PCR. In addition, transferrin receptor 1 and heme oxygenase 1 were induced. We also identified induction of novel genes not previously associated with intestinal iron transport. The Menkes copper ATPase (ATP7a) and metallothionein were strongly induced at all ages studied, suggesting increased copper absorption by enterocytes during iron deficiency. We also found significantly increased liver copper levels in 7- to 12-wk-old iron-deficient rats. Also upregulated at most ages examined were the sodium-dependent vitamin C transporter, tripartite motif protein 27, aquaporin 4, lipocalin-interacting membrane receptor, and the breast cancer-resistance protein (ABCG2). Some genes also showed decreased expression with iron deprivation, including several membrane transporters, metabolic enzymes, and genes involved in the oxidative stress response. We speculate that dietary iron deprivation leads to increased intestinal copper absorption via DMT1 on the brush-border membrane and the Menkes copper ATPase on the basolateral membrane. These findings may thus explain copper loading in the iron-deficient state. We also demonstrate that many other novel genes may be differentially regulated in the setting of iron deprivation.

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“…(ii) Gastrointestinal up-regulation of iron absorption during iron deficiency increases copper absorption (47) and hepatic copper accumulation in rats (48). The increased copper absorption may be mediated by divalent metal transporter 1 (DMT1), which is dramatically up-regulated in iron-deficient duodenum (49).…”

Section: Further Mechanisms By Which Iron Deficiency Can Cause Damage Tomentioning

confidence: 99%

Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats

Walter

Knutson

Paler-Martı́nez

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

304

182

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Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (<5 g͞day) and iron-normal (800 g͞day) rats and in both groups after daily high-iron supplementation (8,000 g͞day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with ironnormal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 g) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 ؋ nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake.

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Influence of nutritional iron deficiency development on some aspects of iron, copper and zinc metabolism

Cited by 18 publications

References 24 publications

Effect of Iron Deficiency on Placental Cytokine Expression and Fetal Growth in the Pregnant Rat1

Effect of Iron Deficiency on Placental Cytokine Expression and Fetal Growth in the Pregnant Rat1

Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum

Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats

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