GABA in brain tissue of paroxysmal (px) chick

An investigation was made of GABA in whole brain and brain regions of paroxysmal (px) chicks. Whole brain levels of GABA were higher (P less than 0.05) in px chicks than in normal siblings by day 10 post-hatching. GABA in brain areas containing degeneration of auditory and vestibular nuclei and tracts was also found to be higher (P less than 0.05) in px chicks. These data indicate that a dysfunction of the GABA pathway occurs early in the px syndrome, possibly as a causative factor.     

Effect of latent iron deficiency on metal levels of rat brain regions

Seven different metals (iron, copper, zinc, calcium, manganese, lead, and cadmium) were studied in eight different brain regions (cerebral cortex, cerebellum, corpus striatum, hypothalamus, hippocampus, midbrain, medulla oblongata, and pons) of weaned rats (21-d-old) maintained on an iron-deficient (18-20 mg iron/kg) diet for 8 wk. Iron was found to decrease in all the brain regions, except medulla oblongata and pons, in comparison to their respective levels in control rats, receiving an iron-sufficient (390 mg iron/kg) diet. Brain regions showed different susceptibility toward iron deficiency-induced alterations in the levels of various metals, such as zinc, was found to increase in hippocampus (19%, p less than 0.05) and midbrain (16%, p less than 0.05), copper in cerebral cortex (18%, p less than 0.05) and corpus striatum (16% p less than 0.05), calcium in corpus striatum (22%, p less than 0.01) and hypothalamus (17%, p less than 0.02), and manganese in hypothalamus (18%, p less than 0.05) only. Toxic metals lead and cadmium also increased in cerebellum (19%, p less than 0.05) and hippocampus (17%, p less than 0.05) regions, respectively. Apart from these changes, liver (64%, p less than 0.001) and brain (19%, p less than 0.01) nonheme iron contents were found to decrease significantly, but body, liver, and brain weights, packed cell volume, and hemoglobin content remained unaltered in these experimental rats. Rehabilitation of iron-deficient rats with an iron-sufficient diet for 2 wk recovered the values of zinc in both the hippocampus and mid-brain regions and calcium in the hypothalamus region only. Liver nonheme iron improved significantly; however, no remarkable effect was noticed in brain nonheme iron following rehabilitation. It may be concluded that latent iron deficiency produced alterations in various metal levels in different brain regions, and corpus striatum was found to be the most vulnerable region for such changes. It is also evident that brain regions were resistant for any recovery in their altered metallic levels in response to rehabilitation for 2 wk.     

Dietary cimetidine and copper in Eimeria acervulina-infected chicks

The effects of varying levels of cimetidine (N"-cyano-N-methyl-N'-(2-[(5-methylimidazol-4-yl)methylthio]-ethyl ) guanidine) on Eimeria acervulina (duodenal coccidiosis)-induced changes in gain, efficiency, duodenal pH, and liver copper concentration of chicks were investigated. In a preliminary trial, gain, efficiency, and duodenal pH were significantly reduced in chicks inoculated one time with 1 X 10(6) sporulated oocysts. Dietary addition of 121 ppm monensin (2-[5-ethyltetrahydro-5-[tetrahydro-3-methyl-5-[tetrahydro-6-hydro xy-6- (hydroxymethyl)-3,5-dimethyl-2H-pyran-2-yl]-2-furyl]-2-furyl]-9-hydroxy- beta-methoxy-alpha, gamma, 2,8-tetramethyl-1,6-dioxaspiro[4.5]decane-7-butyric acid) prevented these coccidiosis-induced aberrations. In subsequent trials, growth rate, feed efficiency, and duodenal pH were reduced by E. acervulina infection, but were unaffected (P greater than 0.10) by dietary addition of 0.01% cimetidine. Linear depressions (P less than 0.05) in gain and efficiency, however, were observed from 0.05 and 0.10% cimetidine additions. Dietary addition of 500 ppm copper increased liver copper levels thirtyfold (P less than 0.01) after 2 weeks. Significant coccidiosis X copper interactions were detected in gain, efficiency, duodenal pH reduction, and liver copper elevation of chicks repeatedly inoculated with 4 X 10(5) sporulated E. acervulina oocysts. Coccidiosis increased liver copper levels (P less than 0.01) of chicks fed excess copper an additional threefold compared with uninfected chicks fed excess copper. Dietary additions of 0.01, 0.05 or 0.10% cimetidine were ineffective in preventing coccidiosis-associated performance and duodenal pH depressions as well as the coccidiosis-induced liver copper elevation. Apparently, host response to cimetidine is minor in comparison to effects of coccidia on duodenal pH. Increased copper solubility at low duodenal pH may explain high tissue copper levels and enhanced copper toxicity due to coccidiosis.     

Biological activity of phenolic compounds. Hepatic cytochrome P-450, cytochrome b5, and NADPH cytochrome c reductase in chicks and rats fed phenolic monomers, polymers, and glycosides

Eight experiments were conducted to determine effects of a phenolic polymer (Kraft wood lignin, Indulin), phenolic glycosides (cane molasses and wood molasses), and phenolic monomers (vanillin, vanillic acid, ferulic acid, and p-coumaric acid) on liver cytochromes P-450, cytochrome b5, and NADPH cytochrome c reductase in chicks and rats. Chicks fed 6.0% lignin had a higher (P less than 0.01) cytochromes P-450 content than did chicks fed 0% fiber, 6.0% wood cellulose (Solka Floc), or 6.0% arenaceous flour. NADPH cytochrome c reductase activity was not affected by treatment. Chicks fed 12.0% wood molasses had a higher (P less than 0.06) cytochromes P-450 level than did chicks fed 0% fiber or 6.0% wood molasses. Cane molasses incorporated at both 6.0 and 12.0% of the diet induced (P less than 0.05) cytochromes P-450 content over those of control-fed birds. Chicks fed 6.0% lignin, with or without antibiotic (bacitracin:neomycin sulfate, 2:1), had a higher (P less than 0.01) cytochromes P-450 level than did chicks fed control diets, with or without antibiotic. Additionally, chicks fed 6.0% lignin had lower (P less than 0.01) intestinal diaminopimelic acid (DAP) levels than did chicks fed 0% fiber. Rats fed 0% fiber, 6.0% wood cellulose, 6.0% arenaceous flour, or 6.0% lignin exhibited no difference in cytochrome level or activity among treatments. Chicks fed 0.5% vanillin, 0.5% vanillic acid, 0.5% ferulic acid, or 0.5% p-coumaric acid had comparable cytochromes level and activity compared with chicks fed no phenolics. Chicks fed 0.5% p-coumaric acid had lower (P less than 0.05) rates of gain than did chicks fed control or other phenolic-containing diets. Rats fed these phenolics had similar cytochromes P-450 content among treatments.     

Effects of triiodothyronine treatments on body and organ growth and the development of immune function in dwarf chickens

The effects of triiodothyronine (T3) treatments on general body growth, long bone growth, primary lymphoid organ development, antibody production, and serum growth hormone (GH) and thyroid hormone levels were examined in two dwarf strains (sex-linked dwarf--SLD, and autosomal dwarf--ADW) and in a normal-growing control strain (K) of White Leghorn chickens. One-day-old male chicks from each of these strains were assigned to either an untreated control group or to one of the groups receiving a T3 supplement ranging from 0.01 to 1.0 ppm. General body growth and long bone growth were significantly (P less than 0.05) stimulated only within the SLD strain by the intermediate T3 dosages. The 1.0-ppm T3 dosage level resulted in depressed body weights within both the K and ADW strains but produced no significant changes within the SLD strain. Thymic growth was significantly stimulated due to treatments of 0.1 ppm T3 in the SLD strain (P less than 0.05) and 1.0 ppm T3 in both the SLD and ADW strains (P less than 0.001 and P less than 0.05, respectively). Bursal growth was significantly depressed (P less than 0.05) at all T3 dosage levels within the SLD strain while 0.01 and 0.1-ppm T3 treatments resulted in significant bursal growth stimulation in the K and ADW strains, respectively. Concomitant with the depressed bursal growth, antibody production was significantly depressed (P less than 0.05) within the SLD strain at the 1.0-ppm T3 dosage level. Antibody production was not significantly affected by any of the T3 treatments within the control K or ADW strains. Serum T3 levels were significantly increased in all strains by the T3 supplementation but thyroxine (T4) serum levels were affected only within the SLD strain. The 0.01-ppm T3 treatment resulted in a significant increase (P less than 0.05) in serum T4 levels within this strain and treatment group. The only increase (P less than 0.05) in GH levels due to T3 treatments occurred within the same SLD treatment group. The higher T3 treatments resulted in serum GH levels being severely depressed (P less than 0.01) in all strains.     

Effect of early feed restriction in male broiler chicks on plasma metabolic hormones during feed restriction and accelerated growth

1. Plasma GH was greater (P less than 0.05) on day 12 in ad libitum-fed birds compared to restricted chicks. Conversely, maximum GH levels were found to occur in the nutrient restricted chicks during the period of accelerated growth (day 42). 2. A significant decline in circulating insulin concentrations with advancing age was evident in both ad libitum-fed and restricted chicks. 3. Feed restriction significantly suppressed circulating T3 in restricted chicks, with concentrations returning to control levels upon refeeding. 4. A significant increase in T4 with advancing age was evident in both treatment groups, with T4 being significantly greater in controls compared to restricted chicks at 54 days of age.     

Tissue Distribution, Metabolism, Anticonvulsant Efficacy, and Effect on Brain Amino Acid Levels of the Glia-Selective γ-Aminobutyric Acid Transport Inhibitor 4,5,6,7-Tetrahydroisoxazolo[4,5-c]pyridin-3-ol in Mice and Chicks

Using tritium-labelled 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) its tissue distribution and metabolism were investigated in adult mice and 4-day-old chicks after systemic administration of the drug. It was found not to be significantly metabolized in the brain since metabolites of THPO corresponding to only approximately 8% of the parent compound could be detected 30 min after administration of the drug intramuscularly in mice. In the liver, however, THPO was found to be metabolized to a considerable extent. In chicks THPO metabolites were found in the brain but they accounted for less than 35% of the radioactivity. The brain concentration of THPO in mice and chicks corresponded to respectively 10 and 50% of the dose injected intramuscularly and the tissue level was essentially constant for at least 3 h after injection. Following systemic administration of THPO to mice and chicks the contents of aspartate, glutamate, glutamine, and gamma-aminobutyric acid (GABA) in whole brain and in synaptosomes was determined. It was found that only GABA contents were affected being increased in synaptosomes from mice and decreased in whole brain in chicks. Doses of THPO, which in chicks but not in mice led to brain levels that were sufficient to inhibit glial GABA uptake, were found to protect chicks but not mice against isonicotinic acid hydrazide-induced seizures. The findings are compatible with the notion that THPO exerts its anticonvulsant activity by inhibition of astrocytic GABA uptake.     

Dietary propylthiouracil and 17 beta-estradiol benzoate implant effects on liver carbohydrate and lipid metabolism in chicks

1. Forty-eight chicks (21 days old) were implanted (+/- 50 mg 17-beta estradiol; EBI) and fed diets containing +/- 0.1% propylthiouracil (PTU) for 7 days to determine the role of gonadal hormones in the regulation of energy metabolism in the hypothyroid chick. 2. In vitro lipogenesis (IVL) and glucose production (NGP) were measured in liver explants. 3. Liver glycogen (GLY) metabolism was studied in particulate fractions (50,000 x g) of liver. 4. Glycogen synthetase activity (GLYSYN) was assayed in the presence of glucose-6-phosphate (G-6P; 0, 0.15 and 10 mM) to determine activation states. 5. PTU and EBI increased (P less than 0.05) both GLY concentration and GLYSYN activity in chicks but, did not increase G-6P activity ratios or the in vitro activation of GLYSYN. 6. Both PTU and EBI increased (P less than 0.05) IVL and NGP. 7. Estradiol magnifies the effects of PTU in chicks suggesting an interaction between thyroid status and gonadal function.     

Reversibility of the effects of dietary fish oil on the fatty acid composition of the brain and retina of growing chicks.

Dietary fish oil increases levels of (n-3) fatty acids in the brain and retina of younger animals but has less effect in adults. The duration of the effects of fish oil in young animals, as well as the extent of reversibility of the effects, are unknown. Laying hens were fed either a fish oil diet or a soybean oil-based control diet. Resulting chicks were assigned to three diet groups: chicks from fish oil and soybean oil hens were continued on fish oil and soybean oil diets, respectively, for 0, 3, 6, or 9 weeks, and additional chicks from the fish oil hens were fed the fish oil diet for 0, 3, or 6 weeks and then reversed to the soybean oil diet for a period of 3 weeks. The fatty acid composition of the brain, retina, liver, and serum of the reversal chicks was compared with chicks fed the fish oil diet only or the soybean oil diet only. Brain levels of docosahexaenoic acid (22:6(n-3)) decreased substantially when reversal from the fish oil diet to the control diet was begun at hatching, but did not decrease when reversal was begun at later times. Other (n-3) fatty acids in the brain, docosapentaenoic acid (22:5(n-3)) and eicosapentaenoic acid (20:5(n-3)), decreased substantially at all ages, and to a greater extent than 22:6(n-3). Brain arachidonic acid (20:4(n-6)), which was low in fish oil chicks, rose to control after reversal at hatching, but recovered only partially when reversal was begun at later times. A similar patterns was observed in the retina. Serum and liver (n-3) fatty acids fell to control in all reversal chicks, and (n-6) fatty acids increased to control, except in chicks reversed at 6 weeks. This study demonstrates that by 3 weeks of age the chick brain strongly resists diet-induced lowering of high levels of 22:6(n-3).     

Globus pallidus: a target brain region for divalent metal accumulation associated with dietary iron deficiency

Recently, iron deficiency has been connected with a heterogeneous accumulation of manganese in the rat brain. The striatum is particularly vulnerable, for there is a significant negative correlation between accumulated manganese and gamma-aminobutyric acid levels. The effect of dietary iron deficiency on the distribution of zinc and copper, two other divalent metals with essential neurobiological roles, is relatively unexplored. Thus, the primary goal of this study was to examine the effect of manipulating dietary iron and manganese levels on the concentrations of copper, iron, manganese and zinc in five rat brain regions as determined with inductively coupled plasma mass spectrometry analysis. Because divalent metal transporter has been implicated as a transporter of brain iron, manganese, and to a lesser extent zinc and copper, another goal of the study was to measure brain regional changes in transporter levels using Western blot analysis. As expected, there was a significant effect of iron deficiency (P < 0.05) on decreasing iron concentrations in the cerebellum and caudate putamen; and increasing manganese concentrations in caudate putamen, globus pallidus and substantia nigra. Furthermore, there was a significant effect of iron deficiency (P < 0.05) on increasing zinc concentration and a statistical trend (P = 0.08) toward iron deficiency-induced copper accumulation in the globus pallidus. Transporter protein in all five regions increased due to iron deficiency compared to control levels (P < 0.05); however, the globus pallidus and substantia nigra revealed the greatest increase. Therefore, the globus pallidus appears to be a target for divalent metal accumulation that is associated with dietary iron deficiency, potentially caused by increased transporter protein levels.     

Iron decreases the nuclear but not the cytosolic content of the neurohormone melatonin in several tissues in chicks

This paper describes the influence of iron on both nuclear and cytosolic melatonin contents in several tissues of chicks. The neurohormone melatonin was estimated by means of radioimmunoassay. Iron, administered as FeCl₃, decreased the nuclear melatonin level in a variety of tissues, including brain, heart, lung, kidney, and erythrocytes (nucleated cells in chicks) but was not seen in either the liver or gut. All variations related with iron were seen in the nuclear fraction, while only in the pineal gland did the melatonin content of the cytosol change as a result of iron treatment. We also observed a day-night rhythm in the nuclear melatonin: high nuclear levels of melatonin at night and low levels during the light period. This is the first report of nuclear localization of melatonin in any avian cell. © 1996 Wiley-Liss, Inc.     

Immunochemical studies on the putative plasmalemmal receptor for 1, 25-dihydroxyvitamin D(3). III. Vitamin D status

The effect of vitamin D status on levels of the putative 1, 25(OH)(2)D(3) membrane receptor (pmVDR) was studied in chick intestine, kidney, and brain. Western analyses and assays for specific [(3)H]1,25(OH)(2)D(3) binding indicated that, in intestine, pmVDR levels were greatest in -D chicks relative to +1,25D and +D animals (P < 0.05). In kidney, protein levels and specific binding followed the order +D > +1,25D, -D. In brain, vitamin D status did not affect protein levels or specific binding levels. In tissue from normal chicks, both protein and specific binding followed the order of intestine > kidney > brain membranes. Intestinal cells were further evaluated for the effect of 1,25(OH)(2)D(3) on selected "rapid responses." Extrusion of (45)Ca in response to 130 pM 1, 25(OH)(2)D(3) in vitro was greater in cells from -D chicks than from +1,25D or normal birds. Analyses of signal transduction events revealed diminished hormone-induced intracellular calcium oscillations (as assessed by fura-2 fluorescence), and lack of steroid-enhanced protein kinase (PK) A activity in intestinal epithelial cells from -D chicks relative to +D chicks. PK C activation by 130 pM 1,25(OH)(2)D(3) was approximately twofold in cells from +D or -D chicks. The combined results indicate that vitamin D status differentially affects the pmVDR in intestine, kidney, and brain. In intestine, vitamin D deficiency differentially affects (45)Ca handling, intracellular calcium oscillations, PK A and PK C activities in response to 1,25(OH)(2)D(3).     

Chicken hepatic metabolism in vitro. Protein and energy relations in the broiler chicken--VI. Effect of dietary protein and energy restrictions on in vitro carbohydrate and lipid metabolism and metabolic hormone profiles

1. Ross male broiler chicks growing from 14 to 28 days of age were fed 14 and 20% protein diets (4 kcal day-1/body wt0.66) or 20 and 28% protein diets (2.8 kcal day-1/body wt0.66) in a 2 x 2 factorial arrangement to determine the effects of protein and energy intakes on in vitro lipogenesis (IVL) and net glucose production (NGP). Plasma concentrations of insulin, glucagon, thyroid hormones (T3 and T4) and somatomedin-C (Sm-C) were estimated by radioimmunoassay. 2. There was a significant (P less than 0.05) decrease in IVL in the chicks given the higher daily protein intake. 3. The higher protein intake increased (P less than 0.05) NGP while the lower energy intake decreased (P less than 0.05) NGP. 4. Insulin, both thyroid hormones and Sm-C were affected by dietary energy and protein intakes.     

Effects of Dietary Selenium, Vitamin E, and Their Combination on Growth, Serum Metabolites, and Antioxidant Defense System in Skeletal Muscle of Broilers Under Heat Stress

This experiment was conducted to evaluate the effects of dietary vitamin E, selenium (Se), and a combination of the two, on the performance, serum metabolites and oxidative stability of skeletal muscle of broilers during heat stress. The broilers raised in either a thermoneutral (23.9°C constant) or heat stress (23.9°C to 37°C cycling) environment were assigned to 6 dietary treatments (0, 0.5, or 1 mg/kg Se; 125 and 250 mg/kg vitamin E; or 0.5 mg/kg Se plus 125 mg/kg vitamin E) from 1 to 49 days of age. At the end of the experiment, blood samples were collected from chicks, the chicks sacrificed, and pectoralis superficialis muscle was used for measurement of malondialdehyde (MDA) concentration and enzyme activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). The heat-stressed chicks consumed less feed, gained less weight, and had higher feed conversion ratio when compared to thermoneutral chicks (P<0.05). Serum concentrations of iron (Fe) and zinc (Zn) were decreased by heat stress (P<0.05), whereas the serum concentrations of copper (Cu), glucose, and uric acid were significantly increased under heat stress (P<0.05). The chicks that received supplemental of vitamin E exhibited significantly higher serum concentrations of Zn (P<0.05) and significantly lower concentrations of Cu, glucose, and uric acid (P<0.05) when exposed to heat stress. Dietary Se also caused a significant decrease in serum glucose, uric acid, and Cu concentrations of heat-stressed broilers (P<0.05), but had no significant effect on Zn concentration (P>0.05). The GPx activity remained relatively constant (P>0.05), though SOD activity and MDA levels in skeletal muscle were enhanced on exposure to heat stress (P<0.05). The heat-stressed chicks that received the combined supplementary level of vitamin E and Se had the lowest concentration of MDA and the highest activity of SOD in the skeletal muscle (P<0.05). Dietary Se also caused a significant increase in enzyme activity of GPx in the skeletal muscle (P<0.05). These results indicate that the derangement of blood parameters and oxidative stability in broilers under heat stress are improved by supplemental vitamin E and Se.     

Effect of Escherichia coli infection on growth and protein metabolism in broiler chicks (Gallus domesticus)

1. A controlled experimental Escherichia coli infection was developed in broiler chicks. 2. Infection with E. coli significantly reduced feed intake, altered growth of the whole body, eviscerated carcass, skeletal muscles, heart and liver. Organ weight and/or the proportions of organs within the body were affected. 3. Protein accumulation in the eviscerated carcass, extensor digitorum communis and sartorius muscles was severely inhibited by infection, and to a greater extent than body weight. 4. Failure of muscle tissue to accumulate protein was associated with a significant decline in protein synthesis, when measured in vitro (-48%; P less than 0.05) and in vivo (-42%; P less than 0.001). Protein degradation also declined (-28.7%), but to a smaller extent than protein synthesis. 5. Although the infected chicks showed no viable bacteria at day 12 after infection, chicks did not reach the same body weight as controls by day 30 after infection.     

Changes in cerebral norepinephrine induced by vibration or noise stress

To investigate the effects of whole body vibration on the central nervous system, rats were exposed to various whole body vibrations and examined for changes in the levels of norepinephrine (NE) in whole brain or regions of the brain. Whole brain NE had decreased significantly (P less than 0.05) after an acceleration of 5.0G with a frequency of 20 Hz; and the decrease was also observed in the hypothalamus (P less than 0.01) and the hippocampus (P less than 0.10). Exposure to noise [100 dB (A)] caused a significant decrease in NE. This decrease related particularly to a significant decrease in midbrain NE (P less than 0.05) and a non-significant decrease of NE in the hypothalamus.     

Prostaglandin-dependent muscle wasting during infection in the broiler chick (Gallus domesticus) and the laboratory rat (Rattus norvegicus).

Systemic infection with Escherichia coli significantly decreased feed intake, slowed growth of the whole body and skeletal muscles, and severely inhibited muscle protein accumulation in both chicks and rats. Treatment with naproxen (6-methoxy-alpha-methyl-2-naphthaleneacetic acid), an inhibitor of prostaglandin production, decreased weight losses of body and muscle, and significantly inhibited muscle protein wasting in infected chicks and rats. E. coli infection increased net protein degradation by 44.8% (P less than 0.05) and prostaglandin E2 production by 148% (P less than 0.05) in isolated extensor digitorum communis muscle from chicks on day 2 after infection. Naproxen treatment significantly decreased net protein degradation and prostaglandin E2 production in infected chicks to values seen in muscles of healthy controls. Quantitatively and qualitatively similar results were seen in isolated rat epitrochlearis muscle.     

Measurement of Lithium-Induced Changes in Mouse Inositol(1)Phosphate Levels In Vivo

An anion-exchange HPLC mass assay was used to characterize Swiss-Webster mouse brain and peripheral tissue inositol(1)phosphate [Ins(1)P]levels. Ins(1)P was identified in all tissues studied but Ins(4)P could be identified only in brain, and then only as a part of a peak containing an additional, unidentified component. As a result, it was not possible to quantify Ins(4)P levels. Following a single subcutaneous dose of lithium (10 mmol/kg), brain Ins(1)P levels were maximally elevated after 6 h (corresponding to peak brain lithium concentrations) and were increased to levels 35- and 20-fold higher than in saline-treated animals in cholinergic agonist (pilocarpine)-stimulated and unstimulated animals, respectively. The ED50 for the lithium-induced accumulation of brain Ins(1)P 6 h after administration was 4-6 mmol/kg. The pilocarpine stimulation of lithium-induced brain Ins(1)P accumulation had an ED50 of 22 mg/kg, with maximal accumulation occurring 120 min after pilocarpine administration. Atropine reduced Ins(1)P levels, in both the absence and the presence of lithium, by 40%, indicating that cholinergic systems contribute a large (40%) component of basal brain phosphatidylinositol (PI) cycle activity. In peripheral tissues, there were lithium-induced accumulations of Ins(1)P in kidney, heart, and liver (but not testes) but these were less than that seen in the brain, suggesting that under basal (and pilocarpine-stimulated) conditions, the brain has a higher turnover of the PI cycle than the various peripheral tissues studied. These data support the hypothesis that lithium exerts its effects in vivo via modulation of the PI cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered metabolic response of iron-deficient women during graded, maximal exercise.

Metabolic responses during a standardized, progressive, maximal work capacity test on a cycle ergometer were studied in 11 women, mean age 28 (SEM 2) years, at admission to the study, after their body iron stores were depleted by diet, phlebotomy and menstruation for about 80 days and after iron repletion by diet for about 100 days, including daily iron supplementation (0.9 mmol iron as ferrous sulfate) for the last 14 days of repletion. Iron depletion was characterized by a decline (P less than 0.05) in hemoglobin, ferritin and body iron balance. Iron repletion, including supplementation, increased (P less than 0.05) hemoglobin, ferritin and iron balance. No changes were observed in cardiovascular and ventilatory responses or peak oxygen uptake. Iron depletion was associated with a reduced (P less than 0.05) rate of oxygen utilization, total oxygen uptake and aerobic energy expenditure, and elevated (P less than 0.05) peak respiratory exchange ratio and post-exercise concentration of lactate. Reduction of body iron stores without overt anemia affects exercise metabolism by reducing total aerobic energy production and increasing glycolytic metabolism.     

Activity-induced adaptations in skeletal muscles of iron-deficient rabbits

The purpose of this study was to determine whether severe iron deficiency alters the adaptive response of skeletal muscle fibers to a sustained increase in tonic contractile activity. Seven weanling rabbits consumed a low iron diet and underwent phlebotomy twice weekly for 6 mo, resulting in severe anemia (mean Hb 5.5 g/dl). Compared with control animals, tibialis anterior skeletal muscles of iron-deficient animals exhibited reduced concentrations of cytochrome c (4.4 +/- 0.7 vs. 8.6 +/- 0.7 nmol/g tissue; P less than 0.01), and reduced activities of citrate synthase (83 +/- 10 vs. 133 +/- 13 mU/mg protein; P less than 0.01) and cytochrome-c oxidase (2.2 +/- 0.2 vs. 3.6 +/- 0.5 U/mg protein; P less than 0.05). In these muscles mitochondria were swollen and displayed deformed cristae. Less severe biochemical abnormalities were observed in cardiac and soleus skeletal muscles. Ten days of continuous electrical stimulation of the motor nerve supplying anterior compartment muscles of iron-deficient rabbits increased expression of mitochondrial proteins: cytochrome c was increased to 154% of control levels (P less than 0.05), and cytochrome-c oxidase and citrate synthase activities were increased to 199 and 272% of control levels, respectively (P less than 0.005). In addition, electrical pacing increased the fractional volume of mitochondria observed by electron microscopy and reduced the activity of aldolase A by 28% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)