Intracardiac iron distribution in newborn guinea pigs following isolated and combined fetal hypoxemia and fetal iron deficiency

1998 ◽  
Vol 76 (9) ◽  
pp. 930-936 ◽  
Author(s):  
Sixto F Gulang III ◽  
Jennifer R Merchant ◽  
Mary A Eaton ◽  
Kelly B Fandel ◽  
Michael K Georgieff
Keyword(s):  
Iron Deficiency ◽  
Cytochrome C ◽  
Guinea Pigs ◽  
Tissue Oxygenation ◽  
Myocardial Tissue ◽  
Fetal Life ◽  
Myocardial Iron ◽  
Fetal Hypoxia ◽  
Iron Deficient ◽  
Hypoxic Group

Myocardial iron deficiency complicates chronic intrauterine hypoxemia during diabetic pregnancies. To understand the effect of both conditions during fetal life on intracardiac iron prioritization, we measured heart myoglobin, cytochrome c, and elemental iron concentrations in six iron-deficient, hypoxic, five iron-sufficient, hypoxic, six iron-deficient, normoxic, and six iron-sufficient, normoxic newborn guinea pigs. The iron-deficient, hypoxic group had lower heart iron (p = 0.03) but higher myoglobin concentration (p < 0.0001) when compared with the iron-sufficient, normoxic group. The percentage of iron incorporated into myoglobin was higher than control in the iron-deficient, hypoxic group (23.2 ± 7.2% vs. 5.2 ± 0.8%; p < 0.001) and increased as total heart iron decreased (r = 0.97; p < 0.001). In contrast, heart cytochrome c concentration was lower than control in the iron-deficient, hypoxic group (p = 0.01), with equal percentages of heart iron incorporated into cytochrome c. This intracellular prioritization of myocardial iron to myoglobin and away from cytochrome c following combined fetal hypoxemia and iron deficiency may represent an adaptive mechanism to preserve myocardial tissue oxygenation, although at the expense of oxidative phosphorylative capability.Key words: fetal, hypoxia, iron deficiency, myoglobin, cytochrome c, heart.

Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration

2005 ◽  
Vol 109 (3) ◽  
pp. 277-286 ◽  
Author(s):  
Feng Dong ◽  
Xiaochun Zhang ◽  
Bruce Culver ◽  
Herbert G. Chew ◽  
Robert O. Kelley ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Cytochrome C ◽  
Nadph Oxidase ◽  
Dietary Iron ◽  
Cytochrome C Release ◽  
Caveolin 1 ◽  
Iron Deficient ◽  
Oxide Synthase ◽  
Cardiac Ultrastructure ◽  
Deficient Group

Iron deficiency is associated with multiple health problems, including the cardiovascular system. However, the mechanism of action of iron-deficiency-induced cardiovascular damage is unclear. The aim of the present study was to examine the effect of dietary iron deficiency on cardiac ultrastructure, mitochondrial cytochrome c release, NOS (nitric oxide synthase) and several stress-related protein molecules, including protein nitrotyrosine, the p47phox subunit of NADPH oxidase, caveolin-1 and RhoA. Male weanling rats were fed with either control or iron-deficient diets for 12 weeks. Cardiac ultrastructure was examined by transmission electron microscopy. Western blot analysis was used to evaluate cytochrome c, endothelial and inducible NOS, NADPH oxidase, caveolin-1 and RhoA. Protein nitrotyrosine formation was measured by ELISA. Rats fed an iron-deficient diet exhibited increased heart weight and size compared with the control group. Heart width, length and ventricular free wall thickness were similar between the two groups. However, the left ventricular dimension and chamber volume were significantly enhanced in the iron-deficient group compared with controls. Ultrastructural examination revealed mitochondrial swelling and abnormal sarcomere structure in iron-deficient ventricular tissues. Cytochrome c release was significantly enhanced in iron-deficient rats. Protein expression of eNOS (endothelial NOS) and iNOS (inducible NOS), and protein nitrotyrosine formation were significantly elevated in cardiac tissue or mitochondrial extraction from the iron-deficient group. Significantly up-regulated NADPH oxidase, caveolin-1 and RhoA expression were also detected in ventricular tissue of the iron-deficient group. Taken together, these results suggest that dietary iron deficiency may have induced cardiac hypertrophy characterized by aberrant mitochondrial and irregular sarcomere organization, which was accompanied by increased reactive nitrogen species and RhoA expression.

Effects of iron deficiency and training on mitochondrial enzymes in skeletal muscle

1987 ◽  
Vol 62 (6) ◽  
pp. 2442-2446 ◽  
Author(s):  
W. T. Willis ◽  
G. A. Brooks ◽  
S. A. Henderson ◽  
P. R. Dallman
Keyword(s):  
Skeletal Muscle ◽  
Iron Deficiency ◽  
Cytochrome C ◽  
Endurance Training ◽  
Tricarboxylic Acid Cycle ◽  
Interactive Effect ◽  
Tricarboxylic Acid ◽  
Mitochondrial Enzymes ◽  
Acid Cycle ◽  
Iron Deficient

We measured mitochondrial enzyme activities in skeletal muscle under conditions of iron deficiency and endurance training to assess the effects of these interventions on the contents and proportions of non-iron-containing and iron-dependent enzymes and proteins. Male Sprague-Dawley rats, 21 days of age, received a diet containing either 6 (iron deficient) or 50 mg iron/kg diet (iron sufficient). At 35 days of age animals were subdivided into sedentary and endurance training groups (running at 0.7 mph, 0% grade, 45 min/day, 6 days/wk). By 70 days of age, iron deficiency had decreased gastrocnemius muscle cytochrome c by 62% in sedentary animals. In contrast, the activities of tricarboxylic acid cycle enzymes were increased, remained unchanged or were slightly decreased, indicating that iron deficiency markedly altered mitochondrial composition. Endurance training increased cytochrome c (35%), tricarboxylic acid cycle enzymes (approximately 15%), and manganese superoxide dismutase (33%) in iron-deficient rats, whereas the same exercise regimen had no effect on the skeletal muscle of iron-sufficient animals. The interactive effect of dietary iron deficiency and mild exercise on mitochondrial enzymes suggests that adaptation to a training stimulus is, to some extent, geared to the relationship between the energy demand of exercise and the capacity for O2 transport and utilization.

Physiological and biochemical effects of iron deficiency on rat skeletal muscle

1981 ◽  
Vol 241 (1) ◽  
pp. C47-C54 ◽  
Author(s):  
J. A. McLane ◽  
R. D. Fell ◽  
R. H. McKay ◽  
W. W. Winder ◽  
E. B. Brown ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Iron Deficiency ◽  
Cytochrome C ◽  
Muscle Fatigue ◽  
Cytochrome Oxidase ◽  
Lactate Concentration ◽  
Respiratory Capacity ◽  
Iron Treatment ◽  
Iron Deficient ◽  
Glycerol 3 Phosphate Dehydrogenase

Young rats were made iron deficient by feeding them a low-iron diet for 8 wk. Iron deficiency resulted in a 50% decrease in cytochrome c and cytochrome oxidase and a 26% decrease in mitochondrial glycerol-3-phosphate dehydrogenase activity in skeletal muscle. Respiratory capacity of muscle homogenates was reduced 55%. After 8 days of iron treatment, respiratory capacity, cytochrome c, cytochrome oxidase, and glycerol-3-phosphate dehydrogenase had returned 50% toward normal. Maximum O2 uptake of contracting hindlimb muscles averaged 8.5 mumol O2.min-1.g-1 in control, 4.3 mumol O2.min-1.g-1 in iron-deficient, and 6.2 mumol O2.min-1.g-1 in the 8-day-iron-repleted rats. Muscle fatigue during 10 min of stimulation was greater in the iron-deficient group. Lactate concentration in red muscle was higher in iron-deficient than in control rats after stimulation. The muscle fatigue and lactate responses returned 50% toward normal during 8 days of iron treatment. We conclude that iron deficiency results in a decrease in skeletal muscle capacity for aerobic metabolism and, by this mechanism, increases susceptibility to fatigue.

scholarly journals Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and Mnemonic Functioning in Women in a Randomized Controlled Trial in India

2017 ◽  
Vol 147 (12) ◽  
pp. 2297-2308 ◽  
Author(s):  
Michael J Wenger ◽  
Laura E Murray-Kolb ◽  
Julie EH Nevins ◽  
Sudha Venkatramanan ◽  
Gregory A Reinhart ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Status ◽  
Controlled Trial ◽  
Reproductive Age ◽  
Deficiency Anemia ◽  
Control Group ◽  
Attention And Memory ◽  
Double Blind ◽  
Iron Deficient ◽  
Mnemonic Function

Abstract Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory. Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function. Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18–55 y. Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function. Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

Is oxygen supply a limiting factor for survival during rewarming from profound hypothermia?

2006 ◽  
Vol 291 (1) ◽  
pp. H441-H450 ◽  
Author(s):  
Timofei V. Kondratiev ◽  
Kristina Flemming ◽  
Eivind S. P. Myhre ◽  
Mikhail A. Sovershaev ◽  
Torkjel Tveita
Keyword(s):  
Blood Volume ◽  
Tissue Oxygenation ◽  
Limiting Factor ◽  
Myocardial Tissue ◽  
Circulating Blood Volume ◽  
Profound Hypothermia ◽  
Group 3 ◽  
Vascular Beds ◽  
Group 2 ◽  
Group 1

It has been postulated that unsuccessful resuscitation of victims of accidental hypothermia is caused by insufficient tissue oxygenation. The aim of this study was to test whether inadequate O2supply and/or malfunctioning O2extraction occur during rewarming from deep/profound hypothermia of different duration. Three groups of rats ( n = 7 each) were used: group 1 served as normothermic control for 5 h; groups 2 and 3 were core cooled to 15°C, kept at 15°C for 1 and 5 h, respectively, and then rewarmed. In both hypothermic groups, cardiac output (CO) decreased spontaneously by >50% in response to cooling. O2consumption fell to less than one-third during cooling but recovered completely in both groups during rewarming. During hypothermia, circulating blood volume in both groups was reduced to approximately one-third of baseline, indicating that some vascular beds were critically perfused during hypothermia. CO recovered completely in animals rewarmed after 1 h ( group 2) but recovered to only 60% in those rewarmed after 5 h ( group 3), whereas blood volume increased to approximately three-fourths of baseline in both groups. Metabolic acidosis was observed only after 5 h of hypothermia (15°C). A significant increase in myocardial tissue heat shock protein 70 after rewarming in group 3, but not in group 2, indicates an association with the duration of hypothermia. Thus mechanisms facilitating O2extraction function well during deep/profound hypothermia, and, despite low CO, O2supply was not a limiting factor for survival in the present experiments.

scholarly journals Impact of Intermittent Apnea on Myocardial Tissue Oxygenation—A Study Using Oxygenation-Sensitive Cardiovascular Magnetic Resonance

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53282 ◽  
Author(s):  
Dominik P. Guensch ◽  
Kady Fischer ◽  
Jacqueline A. Flewitt ◽  
Matthias G. Friedrich
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Tissue Oxygenation ◽  
Myocardial Tissue

Hypothermia in iron deficiency due to altered triiodothyronine metabolism

1980 ◽  
Vol 239 (5) ◽  
pp. R377-R381 ◽  
Author(s):  
E. Dillman ◽  
C. Gale ◽  
W. Green ◽  
D. G. Johnson ◽  
B. Mackler ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Iron Deficiency ◽  
Ambient Temperature ◽  
The Other ◽  
Other Hand ◽  
Iron Deficient ◽  
Catecholamine Response ◽  
Cutaneous Vasoconstriction

Iron-deficient rats become hypothermic and have an excessive catecholamine response when exposed to an ambient temperature of 4 degrees C. This is not due to changes in body insulation, since thickness is unaltered, since differences persist after removal of hair, and since cutaneous vasoconstriction is intact. On the other hand, oxygen consumption of iron-deficient animals at 4 degrees C is reduced, 39 +/- 3 ml . kg-1 . min-1 compared to 63 +/- 2 in control animals. Thyroxine (T4) values at 4 degrees C were 4.34 +/- 0.20 microgram/dl sera as compared to control values of 3.6 +/- 0.32. Triiodothyronine (T3) values of iron-deficient animals in the cold were 48 +/- 6.8 ng/dl as compared to 72 +/- 5.6 in control animals. Treatment of iron-deficient animals with iron was shown to normalize the plasma T3 response at 4 degrees C within 6 days. Thyroidectomized iron-deficient animals injected with T3 did not show hypothermia at 4 degrees C, whereas thyroidectomized iron-deficient animals injected with T4 showed hypothermia, increased catecholamines, and decreased T3 levels as compared to non-iron-deficient animals similarly treated. It is proposed that iron deficiency impairs conversion of T4 to T3 and that this is primarily responsible for the hypothermia observed.

Poor efficacy of oral iron replacement therapy in pediatric patients with heart failure

2021 ◽  
pp. 1-8
Author(s):  
Kriti Puri ◽  
Joseph A. Spinner ◽  
Jacquelyn M. Powers ◽  
Susan W. Denfield ◽  
Hari P. Tunuguntla ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Deficiency ◽  
Transferrin Saturation ◽  
Systolic Heart Failure ◽  
Oral Iron ◽  
Wilcoxon Test ◽  
Iron Therapy ◽  
Oral Iron Therapy ◽  
Iron Deficient ◽  
Iron Replacement

Abstract Introduction: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure. Methods: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test. Results: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy. Conclusions: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

Developmental iron deficiency dysregulates TET activity and DNA hydroxymethylation in the rat hippocampus and cerebellum

2022 ◽  
Author(s):  
Amanda K. Barks ◽  
Montana M. Beeson ◽  
Timothy C. Hallstrom ◽  
Michael K. Georgieff ◽  
Phu V. Tran
Keyword(s):  
Iron Deficiency ◽  
Neural Circuit ◽  
Epigenetic Modification ◽  
Rat Hippocampus ◽  
Dietary Iron ◽  
Deficient Diet ◽  
Dna Hydroxymethylation ◽  
Iron Treatment ◽  
Iron Deficient ◽  
Increased Risk

Iron deficiency (ID) during neurodevelopment is associated with lasting cognitive and socioemotional deficits, and increased risk for neuropsychiatric disease throughout the lifespan. These neurophenotypical changes are underlain by gene dysregulation in the brain that outlasts the period of ID; however, the mechanisms by which ID establishes and maintains gene expression changes are incompletely understood. The epigenetic modification 5-hydroxymethylcytosine (5hmC), or DNA hydroxymethylation, is one candidate mechanism because of its dependence on iron-containing TET enzymes. The aim of the present study was to determine the effect of fetal-neonatal ID on regional brain TET activity, Tet expression, and 5hmC in the developing rat hippocampus and cerebellum, and to determine whether changes are reversible with dietary iron treatment. Timed pregnant Sprague-Dawley rats were fed iron deficient diet (ID; 4 mg/kg Fe) from gestational day (G)2 to generate iron deficient anemic (IDA) offspring. Control dams were fed iron sufficient diet (IS; 200 mg/kg Fe). At postnatal day (P)7, a subset of ID-fed litters was randomized to IS diet, generating treated IDA (TIDA) offspring. At P15, hippocampus and cerebellum were isolated for subsequent analysis. TET activity was quantified by ELISA from nuclear proteins. Expression of Tet1, Tet2, and Tet3 was quantified by qPCR from total RNA. Global %5hmC was quantified by ELISA from genomic DNA. ID increased DNA hydroxymethylation (p=0.0105), with a corresponding increase in TET activity (p<0.0001) and Tet3 expression (p<0.0001) in the P15 hippocampus. In contrast, ID reduced TET activity (p=0.0016) in the P15 cerebellum, with minimal effect on DNA hydroxymethylation. Neonatal dietary iron treatment resulted in partial normalization of these changes in both brain regions. These results demonstrate that the TET/DNA hydroxymethylation system is disrupted by developmental ID in a brain region-specific manner. Differential regional disruption of this epigenetic system may contribute to the lasting neural circuit dysfunction and neurobehavioral dysfunction associated with developmental ID.

In Vivo Neurochemical Characterization of Developing Guinea Pigs and the Effect of Chronic Fetal Hypoxia

2016 ◽  
Vol 41 (7) ◽  
pp. 1831-1843 ◽  
Author(s):  
Wen-Tung Wang ◽  
Phil Lee ◽  
Yafeng Dong ◽  
Hung-Wen Yeh ◽  
Jieun Kim ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Fetal Hypoxia
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