Correlation between birth weight, leptin, zinc and copper levels in maternal and cord blood

Leptin and zinc are involved in the regulation of appetite. Copper is a trace element regulating the functions of several cuproenzymes that are essential for life. To evaluate the relationship between zinc and copper status and the leptin system in humans, we examined whether leptin concentrations in the mother and the newborn correlate with the weight of mother, placenta and newborn. A total of 88 pregnant women at 38-42 weeks' gestation were studied. All infants were categorized as small for gestational age (SGA) (n = 16), average for gestational age (AGA) (n = 59) or large for gestational age (LGA) (n = 13). Leptin, zinc, and copper levels were measured in maternal and cord serum at birth. Maternal BMI and placental weight of the LGA groups were significantly higher than those of the SGA and AGA groups. Cord and maternal leptin levels of the SGA groups were significantly lower than those of the AGA and LGA groups. Maternal serum leptin levels were positively correlated with BMI and maternal zinc levels in all groups. Cord serum leptin levels of all groups were positively correlated with birth weight and placental weight. Birth weight was negatively correlated with maternal and cord copper level of all groups. Umbilical leptin concentrations of SGA newborns correlated with leptin concentrations of their mothers. In all pregnancies, birth weight increases in association with increase in cord leptin level. Our results suggest that maternal zinc but not copper level has an effect on maternal serum leptin levels. The increase in copper level in both maternal and cord blood may contribute to restriction in fetal growth.     

Teratogenesis and low copper status resulting from triethylenetetramine in rats

The teratogenicity of triethylenetetramine (TETA) was studied using the Sprague-Dawley rat. TETA was fed during pregnancy at levels of 0 (control), 0.17, 0.83, or 1.66% in a complete purified diet. The frequency of resorptions and the frequency of abnormal fetuses at term increased with increasing levels of the drug. Maternal and fetal tissue copper levels were significantly lower in the TETA groups than in controls, with levels decreasing in a dose-related manner. Maternal kidney and fetal liver zinc levels increased within the TETA groups in a dose-related manner. Maternal liver iron was increased in the high-dose group compared to controls. Fetal iron concentration and maternal and fetal manganese level were not significantly affected by the drug. These results show that TETA can be a teratogenic agent. Furthermore, the results suggest that the teratogenicity of the drug may be due in part to induction of copper deficiency, and perhaps through induction of zinc toxicity.     

An effect of zinc deficiency on dental caries.

Rat pups suckled by dams fed a zinc-deficient diet developed higher levels of dental caries following a caries-test challenge than pups suckled by dams fed a zinc-adequate diet. The zinc deficient treatment was administered during the mineralization stage of tooth development before the molars erupted. The data shows that suboptimal zinc nutriture was associated with an increase in dental caries.Fluoride, a trace element, is recognized as a factor in preventing dental caries and its use has had a significant impact on dental health in this country. However, the possible roles of other trace elements have not been closely examined. Zinc is a trace element important to bone mineralization as well as in general nutrition.The effects on dental caries produced by the addition of zinc to rat diets have been reported (1, 2, 3). In those investigations, however, zinc supplements were added to diets that were adequate in zinc. Moreover, zinc supplements were fed after the teeth had appeared in the oral cavity. Because the critical period of tooth maturation occurs before eruption (4), post-eruptive zinc supplements probably should not markedly influence the development and, specifically, the mineralization of the tooth. Therefore, we investigated the influence of pre-eruptive zinc deficiency on caries development in rats.     

Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability

The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl₂) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.     

Alterations of Serum Zinc, Copper, Manganese, Iron, Calcium, and Magnesium Concentrations and the Complexity of Interelement Relations in Patients with Obsessive–Compulsive Disorder

The purpose of the present study was to evaluate the status of serum trace elements: zinc, copper, manganese, iron, calcium, and magnesium concentrations in obsessive-compulsive disorder patients. Forty-eight obsessive-compulsive disorder patients and 48 healthy volunteers were included in this study. Patients were recruited from Bangabandhu Sheikh Mujib Medical University by random sampling. Serum trace element concentrations were determined using flame atomic absorption spectroscopy (for zinc, copper, iron, calcium, and magnesium) as well as graphite furnace atomic absorption spectroscopy (for manganese). Data were analyzed using independent t test, Pearson's correlation analysis, regression analysis, and ANOVA. Statistical analysis of these data showed a definite pattern of variation among certain elements in patients with obsessive-compulsive disorder compared to controls. In patients' serum, zinc, iron, and magnesium concentrations decreased significantly (p<0.05) compared to the controls. Serum manganese and calcium concentrations were significantly higher (p<0.05) in patients compared to the controls. These data showed a definite imbalance in the interelement relations in obsessive-compulsive disorder patients compared to controls and therefore suggest a disturbance in the element homeostasis.     

Regulation of the ontogeny of rat liver metallothionein mRNA by zinc

To investigate the role of metals in the regulation of the ontogenic expression of rat liver metallothionein (MT) mRNA, the concentrations of zinc, MT and MT mRNA were determined in livers of fetal and newborn rats from dams which were fed with a control or zinc-deficient or copper-deficient or iron-deficient diet from day 12 of gestation. The liver samples were analyzed for MT-mRNA levels using a mouse MT-I cRNA probe. Although the newborn hepatic levels of each metal (zinc or copper or iron) was specifically reduced corresponding to the respective mineral deficiencies, the hepatic concentrations of total MT and MT-I mRNA were significantly decreased only in pups born from zinc-deficient dams. Injection of the zinc-deficient newborn pups with 20 mg Zn as ZnSO4/kg restored with MT-I mRNA levels to slightly above control values within 5 h of injection. The hepatic zinc, MT and MT-I mRNA levels were observed to increase significantly in control fetal rat liver on days 17-21 of gestation but there were little changes in either zinc or MT in fetal livers from zinc-deficient dams during the late gestational period. The MT-I mRNA level also did not show an increase on days 18 and 20 of gestation in zinc-deficient fetal liver as compared to controls. These results demonstrate a direct role of zinc in hepatic MT gene expression in rat liver during late gestation. Immunohistochemical localization of MT using a specific antibody to rat liver MT showed that the staining for MT in zinc-deficient pup liver was mainly in the cytosol in contrast to the significant nuclear MT staining observed in control newborn rat liver. The results suggest that maternal zinc deficiency has a marked effect not only in decreasing the levels of hepatic MT and MT-I mRNA but also in the localization of MT in newborn rat liver.     

Iron,zinc, and copper content in the tissues of the rat during pregnancy

The levels of iron, zinc, and copper in the tissues of the pregnant rat, on d 12, 19, and 21 after impregnation have been determined and compared with controls. Iron levels decreased considerably in late pregnancy as a result of increased fetal requirements, thus diminishing iron stores in rat tissues, but maintaining the circulating plasma levels. Copper levels increased slightly at midpregnancy, but returned to control levels at the end of gestation. Zinc stores also increased slightly during early pregnancy, yet were decreased at the end of pregnancy, but to a lesser extent than those of iron. The data are explained on the basis of equilibrium between assimilation and fetal needs for copper, a slightly higher demand for zinc with altered equilibrium, and a much altered equilibrium for iron that provokes a dwindling of iron maternal reserves that is not compensated by dietary iron.     

The roles of trace elements in foetal and neonatal development

Manganese, zinc and copper are essential for normal prenatal and neonatal development. Manganese deficiency causes skeletal abnormalities, congenital ataxia due to abnormal inner ear development, and abnormal brain function. Depression of mucopolysaccharide synthesis and manganese superoxide dismutase activity may be fundamental to ultrastructural and other defects. In copper deficiency, neurological and skeletal abnormalities are due to impairment of phospholipid synthesis and collagen crosslinking, and possibly to low activity of copper metalloenzymes. The fundamental defect leading to the extremely teratogenic effects of zinc deficiency is related to depressed synthesis of DNA. In the neonatal period, poor survival and growth and depressed function of the immune system are salient features. Developmental patterns of trace element concentrations in various tissues suggest that important changes in metabolic regulation of trace elements may occur during the neonatal period. This hypothesis is being investigated by studies of molecular localization of trace elements in certain neonatal tissues, in conjunction with similar observations in milk.     

The effect of diabetes on the molecular localization of maternal and fetal zinc and copper metalloprotein in the rat

The molecular localization of maternal and fetal zinc and copper metalloproteins in diabetic and control rats was studied. Compared to controls, liver and kidneys of diabetic dams showed an increased concentration of zinc and copper that was associated with metallothionein. In contrast, fetuses of diabetic dams had lower zinc and metallothionein levels than fetuses from controls. The abnormal maternal trace element metabolism seen with diabetes resulted in alterations of zinc uptake and/or retention of their fetuses.     

Trace element uptake by L-cells as a function of trace elements in a synthetic growth medium

The concentration of trace elements in L-cells has been studied as a function of the trace metal content of the growth medium. Cells were cultured in synthetic media which contained varying trace amounts of the elements manganese, iron, cobalt, copper, zinc and molybdenum. The cellular concentration of the elements potassium, iron, copper and zinc were then determined. It was found that the cell accumulates trace metals at a different rate than they are made available. Deficiencies in zinc could be “induced” in the cell by increasing the concentration of iron, manganese and cobalt; cellular iron deficiencies were observed at larger medium concentrations of zinc, manganese, copper and cobalt. Trace metal uptake by the cell was seen to parallel the utilization by multicellular organisms.     

The effect of variable magnesium intake on potential factors influencing endurance capacity

Rats fed a magnesium (MG) deficient diet have a lower endurance capacity than rats fed Mg adequate diets. The current study evaluates the effects of marginal, moderate, and severe Mg deficiencies on physiological and biochemical changes that may contribute to the reduced endurance capacity of Mg deficient rats. Variable levels of dietary Mg (400, 200, 100, 50 μg/g) were fed for 23 d to 5-wk-old male Osborne-Mendel rats. Indirect blood pressure and heart rate were measured during dietary treatment. Forty-eight hours after an endurance test, rats were killed and sampled for plasma glucose, insulin, and triglyceride levels. Organ weights, mineral and trace element concentrations, and carcass composition were determined. Blood pressure was lower in rats fed 50 and 100 ppm Mg during the first half of the study than in controls (400 ppm Mg). There were no significant differences in blood pressure among groups at the end of the study. Heart rate was not affected by dietary Mg intake. Plasma insulin was lowered by decreasing dietary Mg; however, plasma glucose and triglyceride concentrations were not affected by dietary Mg intake. Rats fed 100 and 50 ppm Mg diets had significantly higher calcium concentrations in plasma and gastrocnemius muscle than controls. Dietary Mg variably affected tissue trace element (iron, zinc, copper, and manganese) concentrations but did not affect Mg concentrations in any organ studied. Body composition was significantly altered by dietary Mg intake. In conclusion, variable Mg intake differentially affects the parameters evaluated. Thus, the decreased endurance capacity of the Mg deficient rat is apparently not the result of a single biochemical lesion but is likely to be multifactorial.     

Assessment of trace elements in human brain using inductively coupled plasma mass spectrometry

Recent brain research reveals a major role of trace elements in various diseases such as multiple sclerosis, Alzheimer's and Wilson's disease. The majority of published tissue concentrations dates back decades, and was assessed with various methods. Little is known about hemispherical differences, the correlation of trace elements or age-dependent changes in the human brain. Thus, the aim of this study was to examine trace element concentrations in different human brain regions after whole brain formalin fixation.549 samples of 13 brain regions were investigated in 11 deceased subjects without known history of brain pathology. Regional wet-to-dry mass ratios and concentrations of iron, copper, magnesium, manganese, calcium and zinc were determined using inductively coupled plasma mass spectrometry.Cortical gray matter revealed higher water content (wet-to-dry mass ratios 5.84–6.40) than white matter regions (wet-to-dry mass ratios 2.95–3.05). Element concentrations displayed specific regional differences. Good linear correlation of concentrations between elements was found for iron/copper as well as for manganese/magnesium (Spearman's rank correlation coefficient 0.74 and 0.65, respectively). Significant inter-hemispherical differences were found for copper in occipital white matter, for magnesium and calcium in putamen and for iron and copper in temporal white matter. An age dependent increase was seen in cortical gray matter for calcium, for magnesium in all regions except in cortical gray matter, for copper in substantia nigra and for zinc in occipital cortex.The presented trace element concentrations can serve as a fundamental basis for further brain research. Wet-to-dry mass ratios allow a comparison with reference data from other studies.     

Trace elements status in multinodular goiter

Importance of iodine and selenium in thyroid metabolism is well known, but the roles of other essential trace elements including copper, zinc, manganese and iron on thyroid hormone homeostasis remain unclear. The aim of this study was to investigate the status of those trace elements in benign thyroid diseases and evaluate possible links between trace element concentrations and thyroid hormones.The study group was composed of 25 patients with multinodular goiter. Concentrations of thyroid hormones (plasma-free thyroxine, FT₄; free triiodothyronine, FT₃; and thyrotropin, TSH), selenium, copper, zinc, manganese and iron in plasma, and urinary iodine were determined. The results were compared with those of a healthy control group (n=20) with no thyroid disorder.A mild iodine deficiency was observed in the patients with multinodular goiter whereas urinary iodine levels were in the range of “normal” values in healthy controls. All patients were euthyroid, and their thyroid hormone concentrations were not significantly different from the control group. Plasma selenium, zinc and iron concentrations did not differ from controls, while copper and manganese levels were found to be significantly higher in the patients with multinodular goiter indicating links between these trace elements and thyroid function and possibly in development of goiter. Besides iodine, there was a significant correlation between plasma copper concentration and FT₃/FT₄ ratio.     

The effect of high dose oral manganese exposure on copper,iron and zinc levels in rats

Manganese is an essential dietary nutrient and trace element with important roles in mammalian development, metabolism, and antioxidant defense. In healthy individuals, gastrointestinal absorption and hepatobiliary excretion are tightly regulated to maintain systemic manganese concentrations at physiologic levels. Interactions of manganese with other essential metals following high dose ingestion are incompletely understood. We previously reported that gavage manganese exposure in rats resulted in higher tissue manganese concentrations when compared with equivalent dietary or drinking water manganese exposures. In this study, we performed follow-up evaluations to determine whether oral manganese exposure perturbs iron, copper, or zinc tissue concentrations. Rats were exposed to a control diet with 10 ppm manganese or dietary, drinking water, or gavage exposure to approximately 11.1?mg manganese/kg body weight/day for 7 or 61 exposure days. While manganese exposure affected levels of all metals, particularly in the frontal cortex and liver, copper levels were most prominently affected. This result suggests an under-appreciated effect of manganese exposure on copper homeostasis which may contribute to our understanding of the pathophysiology of manganese toxicity.     

Zinc, copper, and iron metabolism during porcine fetal development

Zinc, copper, and iron levels in maternal and fetal pig tissues and fluids were measured starting on d 30 of gestation and continuing to term (d 114) at 10-d intervals. Fetal hematocrit increased from a low of 19% on d 30 to 32% by d 50, after which it remained above 30% to term. Amniotic fluid zinc, copper, and iron all reached maximal levels by d 60 of gestation. Maternal serum zinc levels fluctuated little during gestation, but fetal serum zinc concentration was significantly elevated above maternal levels during the second trimester. Fetal serum copper levels were significantly lower than maternal values throughout gestation and this was also the case for ceruloplasmin oxidase activity. Maternal serum iron reached its lowest level by d 80 of gestation when rate of transfer of iron to the developing fetuses was high. Fetal serum iron declined throughout gestation, reaching its lowest level on d 100. In general, fetal liver concentrations of zinc, copper, and iron were higher than the corresponding maternal values throughout gestation. Distinct increases were noted for fetal hepatic zinc and copper concentrations during the second trimester of pregnancy and these were accompanied by increases in cytosolic and metallothionein-bound zinc and copper levels. Maternal hepatic iron declined during the second trimester, reaching its lowest point on d 80, indicative of the shunting of maternal iron reserves to fetal tissues. Fetal kidney metal levels did not demonstrate any distinctive developmental patterns with respect to zinc, copper, or iron concentrations, but a general accumulation of each metal was observed as gestation progressed. The results of this study highlight some of the distinct changes occurring in the metabolism of zinc, copper, and iron in both maternal and fetal tissues and fluids during gestation in the pig. Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other suitable products.     

Concentations of copper, Zinc, and magnesium in sera from patients with idiopathic dilated cardiomyopathy

Trace elements are known to have a key role in myocardial metabolism. The accumulation (cobalt, arsenic, copper) or deficiency (selenium, zinc) of trace elements may be responsible for idiopathic dilated cardiomyopathy. We investigated the trace element concentrations (Cu, Zn, Mg) in sera from patients with dilated cardiomyopathy by atomic absorption spectrophotometry. We observed that patients with dilated cardiomyopathies have higher copper and lower zinc concentrations in serum than healthy controls. The magnesium concentrations of patients did not differ significantly from that of control subjects.     

Changes in trace element concentrations in hair of growing children

Head hair concentrations of zinc, copper, manganese, and iron from a total of 418 subjects (154 male and 264 female) aged between 6 mo and 20 yr were measured mainly with flameless atomic absorption spectrophotometry. Only zinc analysis of a part of the female samples (n=140) were analyzed with inductively coupled plasma-atomic emission spectrometry. The two analytical methods showed close agreement. The mean concentration of copper and manganese were significantly higher in male subjects than in female subjects. The trace element concentrations in hair varied with the subject’s age. Zinc concentration in hair decreased from 6 mo to 14 yr in the male subjects and decreased from 6 mo to 12 yr in the female subjects. Then, the concentrations increased gradually to 20 yr in the both sexes. Age-dependent variations of copper and manganese concentrations in hair showed similar trends to those of zinc. The results of this study suggest that a higher concentration in the diet of these trace elements may be required for growing children, especially in the period of adolescence.     

The relationship between human cytomegalovirus infection and atherosclerosis development

Transport characteristics of essential trace elements as zinc, copper, selenium and iron have been studied in maternal–fetal direction in normal pregnancies, using in vitro perfusion of human placental lobules. Solutions of trace elements corresponding to twice the physiological concentrations were injected (100 l bolus) into the maternal arterial perfusate. Serial perfusate samples were collected every 30 sec from venous outflows for a study period of 5 min. Concentrations of these trace elements and their transport kinetics were determined. Transport fractions (TF) of zinc, copper, selenium and iron averaged 0.21, 0.49, 0.55 and 0.10% of maternal load respectively. Other parameters such as area under the curve, clearance, elimination constant, absorption and elimination rates showed some significant differences between the various elements. Copper and selenium appear to be transported passively in maternal–fetal direction, while for iron and zinc, role of active transport for transfer across the human placental membrane cannot be discounted. We speculate that alterations in copper: zinc TR50 (transport rate for 50% efflux) and TF ratios could serve as useful indicators for assessing placental transport status of these essential elements in complicated pregnancy states.     

Comparative Study of Serum Zinc, Copper, Manganese, and Iron in Preeclamptic Pregnant Women

Preeclampsia complicates 2–8 % of all pregnancies and it is one of the leading causes of maternal mortality and pre-term delivery in the world. Unfortunately, there is scarcity of document discussing the circulating level of several essential trace elements in preeclampsia patients in Bangladesh. The present study was designed to evaluate the serum concentration of four trace elements, namely zinc, copper, manganese, and iron, in preeclamptic pregnant women. The study was conducted as a case–control study with 50 preeclamptic pregnant women as cases and 58 normotensive pregnant women as controls. Obstetric, anthropometric, and clinical data were collected at routine obstetric visits. Serum trace elements were determined by flame atomic absorption spectroscopy. Independent sample t test and Pearson’s correlation test were done for the statistical analysis using the statistical software package SPSS, version 16.0 (SPSS Inc., Chicago, IL). We observed significant differences for gestational age, body mass index, and systolic and diastolic blood pressure between patient and control groups (p?<?0.05). Analysis of serum trace elements explored significantly lower level of all the four elements in preeclampsia patients in comparison to the control group (p?<?0.05). Pearson’s correlation analysis explored that the correlation between serum level of different trace elements was statistically insignificant (p?>?0.05) except the correlation between zinc and iron in preeclampsia patients (p?<?0.05). Establishment of inter-element relationship strongly supports that there was a disturbance in the element homeostasis in patient with preeclampsia. In conclusion, our study suggests that preeclampsia patients have considerably lower level of serum zinc, copper, manganese, and iron compared to the healthy pregnant women.