Iron and zinc concentrations and 59Fe retention in developing fetuses of zinc-deficient rats

Because disturbances in iron metabolism might contribute to the teratogenicity of zinc deficiency, we examined the effect of zinc deficiency on fetal iron accumulation and maternal and fetal retention of 59Fe. Pregnant rats were fed from mating a purified diet containing 0.5, 4.5 or 100 micrograms Zn/g. Laparotomies were performed on d 12, 16, 19 and 21 of gestation. Maternal blood and concepti were analyzed for zinc and iron. Additional groups of dams fed 0.5 or 100 micrograms Zn/g diet were gavaged on d 19 with a diet containing 59Fe. Six hours later maternal blood and tissues, fetuses and placentas were counted for 59Fe. Maternal plasma zinc, but not iron, concentration was affected by zinc deficiency on d 12. Embryo zinc concentration on d 12 increased with increasing maternal dietary zinc, whereas iron concentration was not different among groups. On d 16-21 plasma iron was higher in dams fed 0.5 micrograms Zn/g diet than in those fed 4.5 or 100 micrograms/g, whereas plasma zinc was lower in dams fed 0.5 or 4.5 micrograms Zn/g than in those fed 100 micrograms Zn/g diet. On d 19 zinc concentration in fetuses from dams fed 0.5 micrograms/g zinc was not different from that of those fed 4.5 micrograms/g zinc, and iron concentration was higher in the 0.5 microgram Zn/g diet group. The increase in iron concentration in zinc-deficient fetuses thus occurs too late to be involved in major structural teratogenesis. Although whole blood concentration of 59Fe was not different in zinc-deficient and control dams, zinc-deficient dams had more 59Fe in the plasma fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

An interaction between zinc and vitamin A in pregnant and fetal rats

A possible interaction between zinc and vitamin A metabolism was studied in pregnant rats. Rats were depleted of vitamin A by feeding retinoic acid during growth. At mating, they were fed diets containing 100, 9, or 0.5 microgram/g zinc and were given orally 400, 8, or 0 microgram/kg body weight/day of retinyl palmitate. Low intake of zinc, but not of vitamin A, caused maternal body weight gain, placental weight, and fetal weight all to be low. The number of implantation sites affected and the proportion of fetuses malformed were dependent on intake of both zinc and vitamin A, and there was a significant interaction between these nutrients in regard to both of these parameters. In maternal as well as in fetal animals, plasma and liver zinc concentrations were low in groups fed low levels of zinc, but not in those given low vitamin A. Liver vitamin A values were affected by vitamin A intake but not by dietary zinc concentration. However, plasma vitamin A concentration in both maternal and fetal animals was significantly reduced by low intake of either zinc or vitamin A. There was a significant interaction between these two nutrients in regard to plasma vitamin A. These data indicate an interaction between zinc and vitamin A metabolism possibly at the level of vitamin A mobilization from the liver.     

Influence of zinc deficiency on retinal reductase and oxidase activities in rat liver and testes.

The influence of zinc deficiency on vitamin A metabolism in rats was investigated by assessing two specific enzymes involved in its metabolism viz retinal reductase and retinal oxidase in the liver as well as in the testes. The activity of retinal reductase in the liver was not altered in zinc deficiency. Retinal oxidase activity on the other hand, was increased approximately 1.5 fold over the pair-fed controls. In contrast, both retinal reductase and oxidase in the testes were decreased during zinc deficiency. The effects of zinic deficiency on vitamin A metabolism in the liver could be partly attributed to the secondary effect of reduced food intake and growth. However, the effects seen in the testes on the metabolic enzymes of vitamin A appear to be due to zinc deficiency per se. The liver concentration of vitamin A (microgram/g) as well as total vitamin A (microgram/liver) were higher in the zinc-deficient rats when compared to the zinc-sufficient rats although not significantly different from the pair-fed controls. In aggreement with previous reports, the plasma vitamin A in zinc-deficient rats were found to be markedly lowered compared to zinc sufficient ad libitum controls.     

Effects of marginal zinc deficiency on subclinical lead toxicity in the rat neonate

Influence of maternal dietary zinc intake on tissue distribution of lead and zinc in neonatal rats administered lead acetate by gavage during lactation was examined. Milk from dams fed a marginally deficient diet (6 micrograms Zn/g diet) contained a lower zinc concentration at the beginning of lactation than did that from control dams (30 micrograms Zn/g diet); no differences were seen by d 11 of lactation. Dams fed the deficient diet had lower plasma zinc values in comparison with pair-fed or ad libitum-fed dams and lower femur zinc concentration in comparison with pair-fed dams. Pups suckling marginally deficient dams had lower concentrations of zinc in plasma, femurs and kidneys although hippocampal and cerebellar zinc were unaltered. Body weights of pups from marginally zinc-deficient dams were lower than those from ad libitum-fed dams, but similar to those from pair-fed dams. Lead ingestion had no effect on body weight. Marginally zinc-deficient pups had greater lead accumulation in blood, femurs, hippocampi and cerebella, but not kidney, than did zinc-adequate pups. Marginal zinc deficiency during lactation increases the body lead burden of suckling rats, an effect not attributable to increased transfer of lead into milk in response to suboptimal maternal zinc status.     

Placental transport of retinol in ewes fed high intakes of vitamin A

Twelve ewes were fed retinyl propionate equivalent to 12,000 micrograms retinol/kg body weight per day for the last two trimesters of pregnancy (group fed high vitamin A). Four ewes received a control level of 120 micrograms/kg body weight per day. Indwelling catheters were implanted surgically in fetal jugular veins and carotid arteries. Ewes or fetal lambs received [3H]retinol intravenously, and blood was sampled until parturition. The ewes fed large amounts of vitamin A maintained viable fetal lambs for 6 d less than did controls. Plasma retinyl ester concentrations were elevated in the ewes fed a high level of vitamin A but not in their fetal lambs. Rates of plasma retinol transport and clearance increased with vitamin A intake in ewes and their fetal lambs. Efficiency of placental retinol transport in the group fed high levels of vitamin A was less than one-quarter that for controls. However, placental transport rate was approximately 100 micrograms/d greater than that of controls with an equivalent amount retained by the fetoplacental unit in the group fed high vitamin A. These data indicate that placental transport of retinol is partially regulated. High maternal vitamin A intake results in high retinol transport to the fetus.     

Studies of marginal zinc deprivation in rhesus monkeys: II. Pregnancy outcome

A marginal state of zinc deficiency was induced in the pregnant nonhuman primate, Macaca mulatta, by feeding a diet containing 4 ppm zinc beginning at conception. Pregnancy outcome of marginally zinc-deficient monkeys (ZD) was compared to both pair-fed (PF) and ad libitum fed (AL) control animals (100 ppm zinc). Stillbirths, abortions, and delivery complications were more frequent in both ZD and PF dams than in AL controls; no malformations were detected (maternal plasma zinc was normal during organogenesis). Male ZD neonates weighed significantly less than same sex controls; also, in relation to colony norms, 7/8 ZD males, 2/8 ZD females, and 1/10 PF controls were of low birth weight. Further, plasma zinc and iron levels were lower in ZD neonates than in AL and PF controls. ZD neonates also had reduced muscle tonus. Birth weight and maternal plasma zinc concentration were negatively correlated in ZD group but positively correlated in AL and PF groups. Indeed, maternal plasma zinc concentration alone did not identify a state of zinc deficiency which impaired fetal growth in monkeys.     

Lack of an effect of dietary fructose on severity of zinc deficiency in rats

Because feeding rats diets containing fructose as the carbohydrate source reduces copper and selenium status, we investigated whether the type of dietary carbohydrate also affected indices of zinc status. The experimental design was a 2 X 2 factorial study with the source of dietary carbohydrate (cornstarch or fructose) and the level of dietary zinc (0.7 or 31 micrograms Zn/g) as the variables. The experiment utilized 76 weanling male Sprague-Dawley rats randomly assigned to one of four dietary groups. Animals fed a zinc-deficient fructose diet were allowed to consume the diet ad libitum; all other groups were pair-fed to that group to ensure equivalent nutrient and energy intake. The results of the 29-d study showed that the most sensitive indices of zinc status measured, including growth, survival and the zinc concentrations of plasma, femur and testes, were not affected by the type of dietary carbohydrate. This lack of an effect of fructose on the zinc status of the experimental animals indicates that the ability of fructose to exacerbate copper and selenium deficiencies is specific, rather than representing a generalized effect of this simple sugar on the requirements and/or metabolism of all essential trace elements.     

Vitamin A during lactation: relationship of maternal diet to milk vitamin A content and to the vitamin A status of lactating rats and their pups

We have investigated the effects of maternal vitamin A intake during pregnancy and lactation or during lactation alone on the concentration of vitamin A in rat's milk and on vitamin A levels in plasma and liver of dams and their pups. Groups of Sprague-Dawley rats were fed diets having either a high vitamin A content [15 retinol equivalents (R.E.)/g diet] or a low vitamin A content (0.6 R.E./g) for 42 d, including 7-8 d prior to pregnancy, pregnancy, and for 14 d of lactation. The concentration of vitamin A in milk on d 14 of lactation was significantly greater on the high vitamin A diets [114 +/- 16 micrograms/dl (mean +/- SEM; n = 8) versus 52 +/- 7.3 micrograms/dl (n = 11), P less than 0.005]. However, milk vitamin A concentration on d 1 of lactation did not vary with maternal vitamin A intake during pregnancy. In a second study in which supplementation with vitamin A (30 R.E./g diet) was begun on d 1 postpartum, the milk vitamin A content increased progressively with duration of lactation. Maternal plasma vitamin A concentrations did not differ between rats fed the higher or lower vitamin A diets. However, liver vitamin A concentrations both of dams and of their 14-d-old pups were significantly higher when dams were fed the higher vitamin A diets during pregnancy and/or lactation. The results of these studies indicate that the transfer of vitamin A from mother to offspring by milk and the vitamin A status of dams and their suckling neonates is influenced by maternal vitamin A intake during lactation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of nutrition and autoimmunity. Failure of zinc deprivation to alter autoantibody production when initiated in disease-established mice

Earlier studies have demonstrated that zinc deprivation, when begun in young NZB mice, can retard the development of autoimmunity and result in an increased life span. The present study evaluated the possible benefits of zinc deprivation in NZB mice with established disease, as this model is more relevant to the human patient. Female NZB mice aged 6-8 mo were fed diets containing either 80 micrograms Zn/g and 10 micrograms Cu/g (control) or 1 microgram Zn/g and 10 micrograms Cu/g (zinc-deficient) for 4 mo. In addition, another group was fed a diet containing 1 microgram Zn/g and 100 micrograms Cu/g to determine whether zinc deficiency could be exacerbated by high dietary copper through a competition of copper with zinc at the intestinal level (zinc deficient + high copper). A fourth group of mice was fed the control diet at the same intake as that of the zinc-deficient group in order to control for the inanition associated with zinc deficiency (restricted intake). Regardless of dietary treatment, all mice developed antierythrocyte antibodies at the same rate. At the end of 4 mo, 82% of the control and the restricted-intake groups had survived, whereas the zinc-deficient group had a 38% survival rate and the zinc-deficient + high copper group had a 50% survival rate. These observations show that, in contrast to findings with younger NZB mice, zinc deprivation of adult NZB mice with established autoimmunity will not improve survival. Indeed, severe zinc deficiency increased the mortality rate, demonstrating the need to consider the potential hazards of dietary extremes.     

The teratogenic effect of zinc deficiency and accompanying feeding patterns in mice

The effect of zinc deficiency on fetal development in rats is well established, as also is the importance of the accompanying feeding/fasting cycle on the severity of the zinc-related dysmorphology. Little is known concerning the teratogenesis of zinc deficiency in mice and nothing has been reported with respect to the feeding pattern in this species when fed a zinc-deficient diet. The present studies with pregnant mice (C57BL/6J) revealed them to be acutely sensitive to dietary zinc restriction, with the result that total loss of offspring occurred when the diet contained less than 5 ppm of zinc. Severe teratogenesis accompanied intakes of between 5 and 10 ppm of zinc, but in contrast to rats, no cyclical feeding pattern was evident in mice receiving a zinc-deficient diet, nor was food intake depressed when expressed on a body weight basis. Tissue zinc levels in mice responded to dietary zinc restriction in a manner similar to that reported for rats, with plasma and bone zinc levels being especially sensitive to the zinc intake.     

Low copper and brain abnormalities in fetus from triethylene tetramine dihydrochloride-treated pregnant mouse.

The effects of prenatal triethylene tetramine dihydrochloride (Trien-2HCl) exposure on fetal mice have been investigated on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 ppm as drinking water, ad libitum. At the level of 12,000 ppm, the frequency of total resorption tended to be high and that of fetal viability tended to be low, as compared to controls. Decreased maternal weight was observed in body, but not in liver, at the level of 12,000 ppm. Fetal body and cerebrum weights significantly decreased at the levels of 6,000 and 12,000 ppm; however, fetal liver weight remained unchanged. Maternal serum copper concentration was not affected by the Trien-2HCl. Fetal copper concentrations of liver and cerebrum were significantly lower in the Trien-2HCl-treated groups than in the controls, with levels decreasing in a dose-related manner. When the copper and zinc concentrations in the group treated at 12,000 ppm were compared with those in controls, significant decreases in both metals were observed in placenta but not in maternal liver. Changes in fetal zinc concentration varied by tissues: i.e., an increase in liver and no change in cerebrum. Fetal abnormalities were frequently observed in brain, and the frequency was increased with increasing levels of the Trien-2HCl. These results suggest that fetal brain abnormalities caused by Trien-2HCl may be due in part to induction of copper deficiency, which is almost equivalent to that in brindled mutant mouse.     

Different effects of zinc and copper deficiency on composition of plasma high density lipoproteins in rats

Male Sprague-Dawley rats (six per group) were fed an egg white-based diet containing 0 or 5 micrograms/g Cu with 1, 10, 100 or 1000 micrograms/g Zn. After 6 wk of feeding, the rats were killed, and the tissues were processed for trace element, lipid and lipoprotein analysis. Copper deficiency was associated with a higher concentration of plasma free cholesterol, high density lipoprotein (HDL) cholesterol and HDL apolipoproteins. Plasma total cholesterol was not significantly affected. No significant differences were noted in HDL lipid composition. However, HDL apo E and apo A-I concentrations were higher with copper deficiency. Lecithin:cholesterol acyltransferase (LCAT) was not affected in a consistent manner by copper status. Varying the amount of zinc in the diet did not produce significant changes in plasma total cholesterol, plasma free cholesterol, HDL cholesterol, or HDL apolipoprotein concentrations. However, HDL from zinc-deficient rats were enriched in free cholesterol and depleted in triglycerides. Furthermore, the concentration of HDL apo C increased as the level of dietary zinc increased.     

哺乳期农村乳母乳汁无机元素含量的变化

目的了解哺乳期人乳无机元素含量的变化及其与乳母膳食的关联。方法采用横断面调查方法,收集55名陕西省澄城县农村健康乳母清晨乳样,利用原子吸收分光光度法测定乳汁钙、镁、铁、锰、锌和铜的浓度。采用24小时回顾法进行连续3天膳食调查,计算膳食营养素的摄入量。结果农村乳母乳汁中镁、锌、铜浓度随哺乳期延长明显降低,铁浓度随哺乳期延长而上升。乳母膳食钙摄入量约为钙膳食参考摄入量(DRI)1/3,膳食无机元素的摄入量与人乳相应元素之间无明显相关性。多因素分析表明,乳汁中钙与镁、铁与铜、锰与锌均呈正相关,钙分别与乳脂、铁、锌呈负相关。结论随哺乳期时间延长,成熟乳中镁、锌、铜浓度降低而铁浓度增加,乳母膳食钙的摄入严重不足,乳汁各元素与膳食相应元素之间无关联。     

缺锌对大鼠维生素A代谢的影响

本研究分两批实验观察了缺锌对大鼠维生素A代谢的影响。实验Ⅰ用24头体重55g左右的雄性Wistar大鼠,随机分成缺锌组、对喂组、加锌组,每组8头,实验期为30天,观察指标有摄食量、体重、血清锌、血清维生素A、肝脏维生素A、胫骨锌。结果表明,缺锌严重影响了大鼠生长发育,并使维生素A积聚于肝脏,血液中维生素A的浓度明显减低。实验Ⅱ用48头体重55g左右雄性Wistar大鼠,先喂缺锌饲料30天,造成缺锌状态,再按体重随机分为四组:缺锌组、治疗Ⅰ组、治疗Ⅱ组、治疗Ⅲ组。三个治疗组中每日每头大鼠腹腔注射锌量分别为0.63μmol、1.89μmol、3.85μmol,治疗期为6天,观察指标同实验Ⅰ。结果为,三个治疗组血清锌及维生素A的浓度均明显高于缺锌组,而肝脏中维生素A的浓度均明显低于缺锌组;说明补锌可以使缺锌大鼠动员肝脏中贮存的维生素A进入血液。     

The effect of ethanol consumption on trace mineral status in elderly rats

The effect of ethanol consumption on trace mineral status in 23-month old female rats was investigated. Ethanol was isocalorically substituted for dextrin at 35% of the calories in a liquid diet. Tissue trace minerals were determined by atomic absorption spectrophotometry. Compared to controls, rats consuming ethanol for 30 days had decreased liver concentrations of zinc, iron and magnesium. Other tissues examined were unaffected. Tissue concentrations of copper and manganese and hemoglobin, hematocrit and plasma ceruloplasmin were not different. Histological liver examination revealed fatty infiltration in ethanol treated rats. Decrease of liver concentrations of zinc, iron and magnesium in the absence of cirrhosis is attributed to the effect of ethanol and was not due to lower dietary intake of these minerals in the ethanol consuming animals compared to the controls.     

Effects of zinc deficiency on the oxidation of retinol and ethanol in rats.

The zinc metalloenzyme alcohol dehydrogenase was assayed in subcellular fractions of liver and retina from zinc-deficient and control rats using retinol and ethanol as substrates. When the zinc concentrations of these tissues were reduced because of feeding inadequate dietary zinc, alcohol dehydrogenase was significantly lowered, and the retinol-retinal as well as the ethanol-ethyladehyde conversion was significantly reduced. While in older rats no changes occurred in liver zinc and alcohol dehydrogenase, the retina was more sensitive to the lack of dietary zinc than the liver. Young rats nursed by zinc-deficient dams showed the most severe changes in both tissues. The data suggest that zinc deficiency affects the utilization of vitamin A as well as the catabolism of ethanol.     

Effect of excess L-lysine on rat growth and on plasma and tissue concentrations of copper, iron and zinc

A 28-day feeding study was conducted to test the effect of excess dietary lysine on rat growth and the concentration of copper, iron and zinc in plasma and liver. Young male Sprague-Dawley rats were fed a 10% protein casein diet with or without excess lysine. There were no significant differences in body weight gain, food intake or plasma proteins among the dietary treatment groups. Supplementation of the basal diet with 2.1% L-lysine caused a 53% reduction in hepatic copper and a significant reduction in hepatic iron. The addition of 0.7% or 2.1% lysine to the basal diet caused significant reductions in levels of plasma copper. The 2.1% level of lysine tended to lower the concentration of zinc in plasma. The data suggest that lysine may interfere with the availability of selected minerals by reducing tissue utilization or promoting excretion, or both.     

The effect of different dietary levels of vitamin A on metabolism of copper iron and zinc in the chick

Chicks were fed on diets containing either no added vitamin A or 3300 micrograms/kg or 330,000 micrograms/kg retinol equivalents for 30 d. Concentrations of copper, iron and zinc were higher in liver and lower in plasma at low and high intakes of vitamin A. Haemoglobin, packed cell volume and erythrocyte levels were depressed by both low and high vitamin A intake and could be related to vitamin A levels by quadratic equations. The Zn and Fe levels in erythrocytes and serum albumin and ceruloplasmin were also affected in a similar fashion by low or high vitamin A diets. Hepatic activity of alcohol dehydrogenase (EC 1.1.1.1) and cytochrome oxidase (EC 1.9.3.1) paralleled Zn and Cu concentrations respectively. Superoxide dismutase (EC 1.15.1.1) and hydrolysis of triolein and retinyl palmitate were not correlated significantly with concentrations of metals but were correlated negatively with log vitamin A concentration. No changes in bone concentrations of Cu, Fe or Zn were detected. It is suggest that vitamin A influences metabolism of Cu, Fe and Zn possibly, in part, due to a decrease in secretion of transport proteins by the liver.     

肝硬化病人维生素A、E及某些矿物质营养状况探讨

本文观察了24例肝硬化病人维生素A、E及铁、锌、铜、锰、钙和镁的营养状况。结果显示,肝硬化(代偿期)病人除维生素E外,上述各种营养素的摄入量均显著低于健康对照组;肝腹水病人的摄入量更低。肝硬化(代偿期)病人血清维生素A、E、铁、锌、铜和锰的含量显著低于健康对照组;肝腹水病人血清铜、镁的含量未见明显变化,但血清钙的含量显著下降,其他各项指标的值更低。上述结果提示,肝硬化病人有维生素A、E、铁、锌、锰和钙的不足或缺乏。     

Tin, copper, iron and calcium metabolism of rats fed various dietary levels of inorganic tin and zinc

Three studies were conducted to determine the effects of various dietary levels of tin (less than 1, approximately 100, approximately 200, approximately 500, approximately 2000 micrograms/g diet) and of zinc (approximately 15, approximately 30, approximately 52 micrograms/g diet) on the metabolism of tin, copper, iron and calcium by growing rats. The accumulation of tin in the kidneys and tibias of animals was proportional to dietary exposure. The concentration of tin in the bones of rats fed greater than 100 micrograms Sn/g diet was 5-fold and 20-fold greater than the levels found in kidney and liver, respectively. Rats fed greater than 500 micrograms Sn/g diet had plasma copper levels that were only 13% of control levels and had depressed copper levels in livers and kidneys. The activity of delta-aminolevulinic acid dehydratase in the erythrocytes of rats fed the highest level of tin was 55% of that found in control animals. The amounts, but not the concentrations, of calcium in the tibias of rats fed greater than 100 micrograms Sn/g diet were less than the levels in the bones of control animals. The moderate variations in dietary zinc levels did not affect significantly the levels of minerals in tissues.