scholarly journals Dietary Iron Intake in Excess of Requirements Impairs Intestinal Copper Absorption in Sprague Dawley Rat Dams, Causing Copper Deficiency in Suckling Pups

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 338
Author(s):  
Jennifer K. Lee ◽  
Jung-Heun Ha ◽  
James F. Collins
Keyword(s):  
Iron Supplementation ◽  
Iron Homeostasis ◽  
Dietary Iron ◽  
Sprague Dawley ◽  
Experimental Proof ◽  
Liver Iron ◽  
Copper Absorption ◽  
Hepatic Copper ◽  
Pregnancy And Lactation ◽  
Copper Depletion

Physiologically relevant iron-copper interactions have been frequently documented. For example, excess enteral iron inhibits copper absorption in laboratory rodents and humans. Whether this also occurs during pregnancy and lactation, when iron supplementation is frequently recommended, is, however, unknown. Here, the hypothesis that high dietary iron will perturb copper homeostasis in pregnant and lactating dams and their pups was tested. We utilized a rat model of iron-deficiency/iron supplementation during pregnancy and lactation to assess this possibility. Rat dams were fed low-iron diets early in pregnancy, and then switched to one of 5 diets with normal (1×) to high iron (20×) until pups were 14 days old. Subsequently, copper and iron homeostasis, and intestinal copper absorption (by oral, intragastric gavage with 64Cu), were assessed. Copper depletion/deficiency occurred in the dams and pups as dietary iron increased, as evidenced by decrements in plasma ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1) activity, depletion of hepatic copper, and liver iron loading. Intestinal copper transport and tissue 64Cu accumulation were lower in dams consuming excess iron, and tissue 64Cu was also low in suckling pups. In some cases, physiological disturbances were noted when dietary iron was only ~3-fold in excess, while for others, effects were observed when dietary iron was 10–20-fold in excess. Excess enteral iron thus antagonizes the absorption of dietary copper, causing copper depletion in dams and their suckling pups. Low milk copper is a likely explanation for copper depletion in the pups, but experimental proof of this awaits future experimentation.

scholarly journals Iron Supplementation Confers Protection on Disease Severity in Dextran Sodium Sulfate (DSS)-Induced Colitis in Rats (OR15-05-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Amanda Bries ◽  
Rachel Derscheid ◽  
Paige Curry ◽  
Joe Webb ◽  
Olivia Meier ◽  
...  
Keyword(s):  
Disease Activity ◽  
Iron Supplementation ◽  
Iron Homeostasis ◽  
Iron Status ◽  
Fold Increase ◽  
Deficiency Anemia ◽  
State University ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Funding Sources

Abstract Objectives Koji iron, enriched with FeSO4 (Ultimine®; ULT), is a novel source of supplemental iron. Previously, we reported ULT had similar absorption as ferrous sulfate (FeSO4), while resulting in less reported adverse effects in women. Iron deficiency anemia is a common manifestation of inflammatory bowel disease (IBD) due to malabsorption and gastrointestinal (GI) bleeding. Therefore, the objective of our study was to identify the efficacy of 2 forms of iron supplementation on impaired GI integrity and anemia caused by dextran sulfate sodium (DSS)-induced colitis. Methods Six wk old Sprague Dawley rats (n = 40) were randomly assigned to one of four treatment groups (n = 10/group): 1) Control with no DSS; 2) Control + DSS only (Nfe); 3) DSS + ULT; 4) DSS + FeSO4. Animals were maintained on the AIN-93 G diets for 7 d. Colitis was induced by administering fresh 3.5% (w/v) DSS ad lib throughout the study. Daily iron supplementation (6 mg Fe/kg BW) was provided in a pulverized treat, and disease activity indices were observed (gross bleeding, stool consistency and weight loss). Histological scoring of colonic ulcerations, inflammation and grade were assessed. Iron status indicators and liver hepcidin were detected using ELISA and qRT-PCR, respectively. Results The severity score of IBD was significantly higher in the animals without iron supplementation than those treated with iron (P < 0.0001). Moreover, iron supplementation protected against diminished hemoglobin and hematocrit levels as a result of DSS treatment (P = 0.001 and P = 0.03, respectively); whereas, these parameters were not significantly (NS) different between ULT and FeSO4. Improvement was found with post mortem disease score of DSS-induced rats with ULT compared to FeSO4 and Nfe by 14% and 39%, respectively (NS). Compared to healthy controls, FeSO4 resulted in a 3.5-fold increase in liver hepcidin gene expression, whereas ULT caused no change. Conclusions The results of this study highlight the beneficial effects iron supplementation has on the disease activity evoked by severe GI inflammation. Furthermore, this data suggests ULT attenuates the progression of IBD by supporting iron homeostasis. Additional analyses will explore the possible mechanisms of these results by identifying the systemic inflammation. Funding Sources College of Human Sciences, Iowa State University Collaborative Seed Grant Program.

scholarly journals Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice

2017 ◽  
Vol 313 (4) ◽  
pp. G353-G360 ◽  
Author(s):  
Jung-Heun Ha ◽  
Caglar Doguer ◽  
James F. Collins
Keyword(s):  
Iron Overload ◽  
Copper Deficiency ◽  
Copper Homeostasis ◽  
Dietary Iron ◽  
Iron Loading ◽  
Homeostatic Regulation ◽  
Dietary Copper ◽  
Copper Absorption ◽  
High Iron ◽  
Copper Depletion

High-iron feeding of rodents has been commonly used to model human iron-overload disorders. We recently noted that high-iron consumption impaired growth and caused severe systemic copper deficiency in growing rats, but the mechanism by which this occurred could not be determined due to technical limitations. In the current investigation, we thus utilized mice; first to determine if the same phenomenon occurred in another mammalian species, and second since we could assess in vivo copper absorption in mice. We hypothesized that excessive dietary iron impaired intestinal copper absorption. Weanling, male mice were thus fed AIN-93G-based diets containing high (HFe) (~8,800 ppm) or adequate (AdFe) (~80 ppm) iron in combination with low (~0.9 ppm), adequate (~9 ppm), or high (~180 ppm) copper for several weeks. Iron and copper homeostasis was subsequently assessed. Mice consuming the HFe diets grew slower, were anemic, and had lower hepatic copper levels and serum ceruloplasmin activity. These physiological perturbations were all prevented by higher dietary copper, demonstrating that copper depletion was the underlying cause. Furthermore, homeostatic regulation of copper absorption was noted in the mice consuming the AdFe diets, with absorption increasing as dietary copper decreased. HFe-fed mice did not have impaired copper absorption (disproving our hypothesis), but homeostatic control of absorption was disrupted. There were also noted perturbations in the tissue distribution of copper in the HFe-fed mice, suggesting that altered storage and thus bioavailability contributed to the noted copper deficiency. Dietary iron loading thus antagonizes copper homeostasis leading to pathological symptoms of severe copper depletion. NEW & NOTEWORTHY High-iron feeding is a common experimental method to model human iron-overload disorders in rodents. Here, we show that dietary iron loading causes severe copper deficiency due to perturbations in the homeostatic regulation of intestinal copper absorption and tissue distribution, which may decrease the bioavailability of copper for use in cuproenzyme synthesis. Whether high-dose iron supplementation in humans antagonizes copper homeostasis is worthy of consideration.

Hepatotoxicity Associated with Dietary Iron Overload in Mice

1993 ◽  
Vol 12 (6) ◽  
pp. 463-467 ◽  
Author(s):  
Felix O. Omara ◽  
Barry R. Blakley ◽  
Lusimbo S. Wanjala
Keyword(s):  
Iron Overload ◽  
Iron Supplementation ◽  
Liver Toxicity ◽  
Serum Alkaline Phosphatase ◽  
Iron Concentration ◽  
Elevated Serum ◽  
Suitable Model ◽  
Dietary Iron ◽  
Liver Iron ◽  
Splenic Macrophages

1 Weanling male CD-1 mice were fed 120 (control), 5000 and 8000 mg of iron kg-1 for seven weeks. The haematocrit ( P=0.265), water consumption ( P=0.170) and percentage body weight ratios of kidney, spleen and heart were not affected by iron supplementation. 2 Iron supplementation reduced weight gain ( P=0.023), increased weight of liver ( P=0.0001), the iron deposition index and concentration of iron in the liver ( P<0.01). A strong correlation between liver iron concentration and level of iron in the diet ( r=0.989) was observed. Histologically, the deposition of iron was restricted to the hepatocytes, Kupffer cells and splenic macrophages. 3 Consumption of 5000 and 8000 mg of iron kg-1 resulted in hepatic damage, as judged by elevated serum alkaline phosphatase and alanine aminotransferase activities ( P<0.05). 4 This study indicates that prolonged feeding of excess dietary iron has the potential to cause hepatic accumulation of iron with resultant liver toxicity, and that mice may be a suitable model to study the mechanisms of dietary iron overload.

Concentration of Liver Iron in Calves and Response to Dietary Iron and Desferrioxamine

1968 ◽  
Vol 27 (5) ◽  
pp. 1426 ◽  
Author(s):  
G. J. St-Laurent ◽  
G. J. Brisson
Keyword(s):  
Dietary Iron ◽  
Liver Iron

scholarly journals Altered Gut Microbiota and Its Metabolites in Hypertension of Developmental Origins: Exploring Differences between Fructose and Antibiotics Exposure

2021 ◽  
Vol 22 (5) ◽  
pp. 2674
Author(s):  
Chien-Ning Hsu ◽  
Julie Y. H. Chan ◽  
Kay L. H. Wu ◽  
Hong-Ren Yu ◽  
Wei-Chia Lee ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Negative Impact ◽  
Short Chain Fatty Acids ◽  
Normal Diet ◽  
Male Offspring ◽  
Sprague Dawley ◽  
Minocycline Treatment ◽  
High Fructose ◽  
Induced Hypertension ◽  
Pregnancy And Lactation

Gut microbiota-derived metabolites, in particular short chain fatty acids (SCFAs) and their receptors, are linked to hypertension. Fructose and antibiotics are commonly used worldwide, and they have a negative impact on the gut microbiota. Our previous study revealed that maternal high-fructose (HF) diet-induced hypertension in adult offspring is relevant to altered gut microbiome and its metabolites. We, therefore, intended to examine whether minocycline administration during pregnancy and lactation may further affect blood pressure (BP) programmed by maternal HF intake via mediating gut microbiota and SCFAs. Pregnant Sprague-Dawley rats received a normal diet or diet containing 60% fructose throughout pregnancy and lactation periods. Additionally, pregnant dams received minocycline (50 mg/kg/day) via oral gavage or a vehicle during pregnancy and lactation periods. Four groups of male offspring were studied (n = 8 per group): normal diet (ND), high-fructose diet (HF), normal diet + minocycline (NDM), and HF + minocycline (HFM). Male offspring were killed at 12 weeks of age. We observed that the HF diet and minocycline administration, both individually and together, causes the elevation of BP in adult male offspring, while there is no synergistic effect between them. Four groups displayed distinct enterotypes. Minocycline treatment leads to an increase in the F/B ratio, but decreased abundance of genera Lactobacillus, Ruminococcus, and Odoribacter. Additionally, minocycline treatment decreases plasma acetic acid and butyric acid levels. Hypertension programmed by maternal HF diet plus minocycline exposure is related to the increased expression of several SCFA receptors. Moreover, minocycline- and HF-induced hypertension, individually or together, is associated with the aberrant activation of the renin–angiotensin system (RAS). Conclusively, our results provide a new insight into the support of gut microbiota and its metabolite SCAFs in the developmental programming of hypertension and cast new light on the role of RAS in this process, which will help prevent hypertension programmed by maternal high-fructose and antibiotic exposure.

Effect of dietary iron supplementation on the course of Plasmodium chabaudi malaria in weanling mice

2000 ◽  
Vol 20 (8) ◽  
pp. 1193-1199
Author(s):  
G.S. Ribeiro ◽  
M.R. Garnica ◽  
M.A. Cardoso ◽  
C. Colli ◽  
H.F. Andrade ◽  
...  
Keyword(s):  
Iron Supplementation ◽  
Dietary Iron ◽  
Plasmodium Chabaudi

Hepcidin inhibition improves iron homeostasis in ferrous sulfate and LPS treatment model in mice

Drug Research ◽  
2021 ◽  
Author(s):  
Vishal Patel ◽  
Amit Joharapurkar ◽  
Samadhan Kshirsagar ◽  
Maulik Patel ◽  
Hiren Patel ◽  
...  
Keyword(s):  
Ferrous Sulfate ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
The Body ◽  
Rapid Screening ◽  
Iron Dextran ◽  
Liver Iron ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
Lps Treatment

Abstract Background Hepcidin, a liver-derived peptide, regulates the absorption, distribution, and circulation of iron in the body. Inflammation or iron overload stimulates hepcidin release, which causes the accumulation of iron in tissues. The inadequate levels of iron in circulation impair erythropoiesis. Inhibition of hepcidin may increase iron in circulation and improve efficient erythropoiesis. Activin-like kinase (ALK) inhibitors decrease hepcidin. Methods In this work, we have investigated an ALK inhibitor LDN193189 for its efficacy in iron homeostasis. The effect of LDN193189 treatment was assessed in C57BL6/J mice, in which hepcidin was induced by either ferrous sulfate or lipopolysaccharide (LPS) injection. Results After two hours of treatment, ferrous sulfate increased serum and liver iron, serum hepcidin, and liver hepcidin expression. On the other hand, LPS reduced serum iron in a dose-related manner after six hours of treatment. LDN193189 treatment increased serum iron, decreased spleen and liver iron, decreased serum hepcidin and liver hepcidin expression in ferrous sulfate-treated mice, and increased serum iron in LPS-induced hypoferremia. We observed that ferrous sulfate caused a significantly higher increase in liver iron, serum hepcidin, and liver hepcidin than turpentine oil or LPS in mice. Iron dextran (intraperitoneal or intravenous) increased serum iron, but LDN193189 did not show hyperferremia with iron dextran stimulus. Conclusion Ferrous sulfate-induced hyperferremia can be a valuable and rapid screening model for assessing the efficacy of hepcidin inhibitors.

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