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Biomedical subjects

B Lönnerdal

Publications and source records attributed to B Lönnerdal.

At least 235 records · Page 13Linked to original sources

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.

Abnormalities, Drug-Induced↗

Teratogenic effects of D-penicillamine in rats: relation to copper deficiency.

The teratogenicity of D-penicillamine (DP) (dimethyl cysteine) was studied using the Sprague-Dawley rat. D-Penicillamine was fed during pregnancy at a level of 0 (control), 0.17, 0.83, or 1.66% of the diet. The frequency of resorptions, and the frequency and severity of malformations, increased with increasing levels of the drug. Maternal and fetal tissue copper levels were significantly lower in the DP groups than in controls, with the levels decreasing in a dose-related manner. Maternal and fetal zinc levels were lower in the 1.6% DP group than in controls. Maternal liver iron concentration was higher in the drug-fed rats than in controls, increasing in a dose-related manner. Fetal iron concentration was not consistently affected by the drug. Maternal and fetal manganese, calcium, and magnesium concentrations were similar among all groups. These results suggest that the teratogenicity of D-penicillamine may be due in part to induction of copper deficiency and, at high dose levels, zinc deficiency, caused by its chelating properties.

Animals↗

The effect of copper supplementation on the teratogenic effects of triethylenetetramine in rats.

Previous research from this laboratory has shown that triethylenetetramine (TETA) fed to rats throughout pregnancy at 0.83% or 1.67% of the diet is teratogenic and results in low copper and high zinc levels in material and fetal tissues. These results suggested that the teratogenic effects of TETA were due to copper deficiency and/or zinc toxicity induced by the drug. In the present study, dams were fed TETA in a control (5 micrograms copper/gm) or copper supplemented (50 micrograms copper/gm) diet throughout pregnancy. Fetuses were removed on day 21 of gestation and examined for abnormalities. Copper supplementation reduced the teratogenicity of TETA; the reduction was correlated with an increase in maternal and fetal tissue copper levels. Copper supplementation did not alter the effects of TETA on tissue zinc levels. Thus TETA teratogenicity appears to be due primarily to induced copper deficiency, which may be reduced by dietary copper supplementation.

Animals↗

Aspects of trace element interactions during development.

The origins of nutritional trace element deficiencies are summarized. Inadequate intake results in primary deficiency, whereas secondary or conditioned deficiencies can arise in several ways including trace element interactions. Evidence is presented and discussed for interactions of essential trace elements during prenatal and early postnatal development. Diets of widely different zinc and copper concentrations and ratios were fed to pregnant rats. Analysis of fetal outcome and copper and zinc concentrations of maternal and fetal livers showed that although there is an interaction between these metals it occurs only at levels of dietary copper deficiency. Iron and manganese interact so that high levels of one depress absorption of the other. Mice fed iron-supplemented diets had liver manganese concentrations lower than those of unsupplemented mice. Iron supplements at high but not low levels also depressed absorption of zinc. Conversely, zinc deficiency in pregnant rats caused higher than normal concentrations of iron in maternal and fetal liver. Trace element analyses of proprietary infant formulas indicate that in some, concentrations and ratios of these trace elements may be incorrect. The effects of essential trace element interactions during development should be further investigated. Caution is urged in considering levels of trace element supplements during pregnancy, lactation, or early childhood.

Animals↗

Teratogenesis and low copper status resulting from D-penicillamine in rats.

The teratogenicity of D-penicillamine was studied using the Sprague-Dawley rat. Fetuses from rats fed diets containing 0.83% D-penicillamine during pregnancy had a high incidence of malformations. Maternal and fetal tissue copper levels were significantly lower in the D-penicillamine group than in controls, suggesting that the teratogenicity of the drug may be due in part to the induction of copper deficiency by its chelating properties.

Abnormalities, Drug-Induced↗

Zinc, copper, calcium, and magnesium in human milk.

Human milk was fractionated and analyzed for the distribution of copper, zinc, calcium, and magnesium among various fractions. In whole milk the concentration of copper was 0.27 +/- 0.13 micrograms/ml, zinc 1.10 +/- 1.19 microgram/ml, calcium 241.2 +/- 61.9 microgram/ml, and magnesium 41.4 +/- 15.2 micrograms/. Most of the Cu, Zn, Ca, and Mg was found in the skim milk, but significant amounts of Cu, Zn, and Ca were found in the fat, most likely associated with the fat globule membrane. Less than 4% of each of the elements was found in the casein. A low molecular weight fraction contained 26% of total Cu. 25% of Zn, 34% of Ca, and 54% of MG. Gel filtration demonstrated Zn and Cu in skim milk binding to two different proteins with molecular weight (MW) greater than 400,000 and 60 to 80,000, as well as to LMW compounds. The unique distribution and binding of these elements in the milk may, in part, explain the known high bioavailability of trace elements and minerals in human milk.

Biological Availability↗

Effect of sample preparation on analysis of superoxide dismutase activity and isoenzymes.

The effect of superoxide dismutase (SOD) activity and isoenzyme pattern of detergents, incubation time, and sonication in the preparation of rat liver samples was investigated. The activity of the manganese form of the enzyme (Mn-SOD) was found to decrease significantly after 4 hr of incubation at room temperature, and activity of the copper, zinc form of the enzyme (Cu, Zn-SOD) was not changed significantly even after 24 hr, although levels were somewhat decreased. Sonication of the sample did not affect Cu, Zn-SOD activity, but total Mn-SOD activity was increased. Addition of detergents did not increase Mn-SOD activity when homogenates were sonicated, indicating that Mn-SOD is not membrane bound. Detergents also had no effect on Cu, Zn-SOD activity. None of the treatments investigated altered the isoenzyme patterns, providing evidence that these isoenzymes are not degradation products.

Animals↗

Picolinic acid in milk, pancreatic juice, and intestine: inadequate for role in zinc absorption.

Picolinic acid (PA) was measured by high pressure liquid chromatography in human milk and other fluids and tissues. Skimmed human milk, intestinal homogenates from human infants and rats, and human and rat pancreatic juice were ultrafiltered and analyzed by high pressure liquid chromatography using an anion-exchange column. Identity of sample components was verified by comparing retention times with those of pure nicotinic acid and PA. The detection limit for PA was 2.5 microM. Human milk contained less than 3.7 microM PA. PA was undetectable in human infant or rat intestine or in human or rat pancreatic juice. The extremely low concentration of PA in milk and its apparent absence in pancreatic juice and intestine provide additional evidence that PA is not the low molecular weight zinc binding ligand of human milk and that it does not have an important physiological role in intestinal zinc absorption.

Animals↗

Zinc and copper binding proteins in human milk.

The proteins binding zinc and copper in human milk have been fractionated and identified, and the distribution of these trace elements among the different binding compounds has been determined. Casein was separated by ultracentrifugation and was found to contain 14% (range 5 to 21%) of the total zinc content in the milk and 28% (range 7 to 48%) of the total copper. Another zinc- and copper-binding protein was isolated by gel filtration and ion-exchange chromatography and identified as serum albumin by gel electrophoresis. Serum albumin in breast milk binds 28% of total zinc and 39% of total copper. The remainder of Zn and Cu was found to be in a low molecular weight form (29% (range 24 to 36%) of Zn; 24% (range 15 to 47%) of Cu) or associated to the fat (29% (range 20 to 45%) of Zn; 9% (range 1 to 21% of Cu). It is hypothesized that association constants of the different binding compounds as well as their concentrations will determine the relative distribution of zinc and copper among them and may affect bioavailability of these elements for the infant.

Breast Feeding↗

Metal ion content of dolichos biflorus lectin and effect of divalent cations on lectin activity.

The metal ion content of the Dolichos biflorus seed lectin has been determined by using atomic absorption spectrophotometry. Ca2+, Mg2+, Mn2+, Zn2+, and Cu2+ were all found in the native lectin and could be removed to different degrees by using a variety of techniques such as high ionic strength, low pH, chelating agent, and combinations of these procedures. By use of affinity electrophoresis, the remaining binding capacity of the lectin could easily be determined, and the D. biflorus lectin showed an absolute requirement for divalent cations to be able to bind N-acetyl-D-galactosamine. The association constant (Ka) of the lectin for N-acetyl-D-galactosamine was determined after remetallization of the lectin with each individual metal ion and a combination of them. The Ka of the lectin for the hapten differed depending on which divalent cation had been used for remetallization. Ca2+ ion alone was equal to a combination of all metal ions in its ability to confer the highest binding activity of the lectin for N-acetyl-D-galactosamine. The other cations, Mg2+, Mn2+, Zn2+, and Cu2+, could not restore the binding activity of the lectin to the same degree as Ca2+ or a combination of all ions. The D. biflorus lectin is, therefore, one of the first lectins that has been shown to require only a single cation to fully retain its binding activity in contrast to most lectins that require a combination of Ca2+, Mn2+, Mg2+, or Zn2+. Furthermore, we have shown that there is a selective process of ion uptake into the lectin since the metal ion ratios in the native lectin compared to the whole seed are quite different.

Cations, Divalent↗

Developmental changes in composition of rat milk: trace elements, minerals, protein, carbohydrate and fat.

The concentrations of iron, copper, zinc, manganese, calcium and magnesium, as well as protein, carbohydrate and fat, were analyzed in rat milk during the course of lactation in rats fed a purified diet. As serial milking has been demonstrated to affect milk composition (1), lactating rats were milked only once at various times from days 0 to 28 after parturition. Concentration of iron decreased rapidly from 9 to 5 micrograms/ml during the 1st week of lactation and changed little thereafter. Similarly, copper concentration decreased considerably in early lactation, from 9 to 2 micrograms/ml, but then remained constant. Zinc concentration did not decrease during the 1st week of lactation, but dropped from 14 micrograms/ml in the 2nd week of lactation to 8-10 micrograms/ml in mature milk. Manganese was unique as its concentration decreased during the early days of lactation, from 0.3 to 0.1 microgram/ml, with a subsequent rise in late lactation back to 0.3 microgram/ml. Calcium and magnesium concentrations increased somewhat in early lactation and decreased slightly in later lactation, but the changes were fairly small as compared to the trace elements. Developmental patterns for protein, carbohydrate and fat were not very pronounced, although protein and carbohydrate increased somewhat in early lactation and later decreased. These data demonstrate that the nutrient intake of the suckling changes markedly during the early neonatal period. These changes should be taken into account in evaluating data on the trace element composition of tissues of suckling rats.

Animals↗