Showing papers in "Biological Trace Element Research in 1991"

Lead-induced tissue fatty acid alterations and lipid peroxidation.

Abstract: Previous work showed that dietary lead (Pb) increases the relative concentration of arachidonic acid (20∶4) as a percentage of total fatty acids, and decreases the relative proportion of linoleic acid (18∶2) to arachidonic acid (18∶2/20∶4) in chick liver, serum, and erythrocyte membranes. The present investigation was undertaken to examine the time-course and magnitude of the fatty acid alterations with increasing dietary Pb levels. We also examined the effects of Pb on the fatty acid composition and lipid peroxide content of hepatic subcellular organelles. In Exp. 1, chicks were fed diets containing 0, 62.5, 125, 250, 500, or 1000 ppm added Pb (as Pb acetate trihydrate) from 1 to 21 d of age. After 21 d, no growth effects were observed; however, Pb lowered the 18∶2/20∶4 ratio and increased 20∶4 concentration in total liver and serum lipids, and in total hepatic phospholipids in a dose-dependent manner. Hepatic mitochondrial membrane fatty acids were not altered, nor was there any increase in hepatic lipid peroxidation. In Exp. 2, chicks were fed diets containing 0, 500, 1000, or 2000 ppm added Pb from 1 to 21 or 22 d of age. Pb depressed growth in a dose-dependent manner. In addition, Pb lowered the 18∶2/20∶4 ratio and increased 20∶4 concentration in total liver lipids and in hepatic mitochondrial and microsomal membranes in a dose-dependent manner. Total hepatic lipid peroxidation was increased over control values by 1000 ppm Pb, and hepatic microsomal lipid peroxidation was increased by dietary Pb levels of 1000 and 2000 ppm. In Exp. 3, body weight, hepatic microsomal lipid peroxidation, and fatty acid composition were determined in 4-, 9-, 14-, 18-, and 23-d-old chicks fed 0 or 1500 ppm added Pb. Body weights of Pb-treated chicks were significantly lower than those of control chicks by day 18. Microsomal 20∶4 concentration and peroxidation increased, and the 18∶2/20∶4 ratio decreased with age in both groups, but the changes were of greater magnitude in the Pb-treated chicks. The results suggest that some of the manifestations of Pb toxicity may be a reflection of increased concentration of 20∶4 in specific membranes. Further, since the Pb-induced alterations in fatty acid composition were noted in the absence of any growth depression, we propose that fatty acid composition is more sensitive than growth rate to the presence of lead in the diet.

A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China.

Abstract: The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People’s Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 μg Se in form of selenized, yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 μg of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.

Minor and Trace Elements in Human Milk from Guatemala, Hungary, Nigeria, Philippines, Sweden, and Zaire Results from a WHO/IAEA Joint Project

Abstract: Concentrations of As, Ca, Cd, Cl, Co, Cr, Cu, F, Fe, Hg, I, K, Mg, Mn, Mo, Na, Ni, P, Pb, Sb, Se, Sn, V, and Zn were determined in human whole milk samples from Guatemala, Hungary, Nigeria, Phillippines, Sweden, and Zaire; in most of these countries, three groups of subjects representing different socioeconomic conditions were studied. Analytical quality control was a primary consideration throughout. The analytical techniques used were atomic absorption spectrophotometry, atomic emission spectrometry with an inductively coupled plasma, colorimetry, electrochemistry, using an ionselective electrode and neutron activation analysis. The differences between median concentrations of Ca, Cl, Mg, K, Na, and P (minor elements) were lower than 20% among the six countries. Among trace elements, concentrations observed in Filipino milk for As, Cd, Co, Cr, Cu, F, Fe, Mn, Mo, Ni, Pb, Sb, Se, and V were higher than for milk samples from other countries. The remaining five countries showed a mixed picture of high and low values. In the case of at least some elements, such as, F, I, Hg, Mn, Pb, and Se, the environment appears to play a major role in determining their concentrations in human milk. The nutritional status of the mother, as reflected by her socioeconomic status, does not appear to influence significantly the breast milk concentrations of minor and trace elements. Significant differences exist between the actual daily intakes observed in this study and current dietary recommendations made by, for example, WHO and the US National Academy of Sciences. These differences are particularly large (an order of magnitude or more!) for Cr, F, Fe, Mn, and Mo; for other elements, such as, Ca, Cu, Mg, P, and Zn, they amount to at least a factor 2. In the opinion of the present authors, these findings point to the need for a possible reassessment of the dietary requirements of young infants, with respect to minor and trace elements, particularly for the elements Ca, Cr, Cu, F, Fe, Mg, Mn, Mo, P, and Zn.

Effect of boron on vitamin D deficient rats

Abstract: The effects of different levels of dietary boron were determined in vitamin D deficient rats. Vitamin D deficient diets containing either 0.158 ppm or 2.72 ppm of boron were fed to rats for 11 w, and calcium, magnesium, and phosphorus apparent absorption and balance were measured in the twelfth week. Higher apparent absorption and balance values for calcium and phosphorus were observed in the rats with higher dietary boron, but very few differences were seen in body wt, organ wt, and bone parameters. Balance measurements represented the present status of the rats after 12 w on the diets, but other measurements represented an accumulation over the lifetime of the rat, including a suckling period with ample vitamin D and boron. The data demonstrated that when rats are vitamin D deficient, as indicated by hypocalcemia, the level of boron in the diet affects mineral balance.

Chronic effects of cadmium on kidney, liver, testis, and fertility of male rats.

Abstract: Male Wistar rats (n:20), at 5 wk of age, were given cadmium in drinking water (10 mg/L water) for 52 wk; 8 males and 20 female rats, as controls, were given tap water. At the end of 28 and 40 wk, some of the cadmium-treated males and control group male rats were sacrificed for the histopathological examination of testis, kidney, and liver. At the end of 56 wk, histopathological examinations were performed in the same way. Liver, kidney, and testis cadmium levels were also determined by atomic absorption spectrophotometry. All the cadmium-treated male rats showed pathological testicular alterations, and liver and kidney damage after chronic exposure. Cadmium levels were found to be highest in the kidney (1.009 +/- 0.034 microgram/g wet tissue in the infertile group). At the end of the 52-wk period, reproductive capacity of the cadmium-treated rats was investigated and was found to be lost in 39.89% of the animals.

Nephrotoxicity and neurotoxicity in humans from organogermanium compounds and germanium dioxide

Abstract: There is no known biological requirement for germanium (Ge), germanates, or any organogermanium compound. Ge deficiency has not been demonstrated in any animal. The estimated average dietary intake of Ge in humans is 1.5 mg/d. Ge is widely distributed in edible foods, all of which, with few exceptions, contain less than 5 ppm Ge, since higher levels are toxic to most plants. Ingestion of Ge compounds has been shown to produce toxic effects in experimental animals. In recent years inorganic germanium salts and novel organogermanium compounds, such as carboxyethyl germanium sesquioxide (Ge-132) and lactate-citrate-germanate (Ge lactate citrate) have been sold as "nutritional supplements" in some countries for their purported immunomodulatory effects or as health-producing elixirs, resulting in intakes of Ge significantly exceeding the estimated average dietary intake. Since 1982, there have been 18 reported cases of acute renal dysfunction or failure, including two deaths, linked to oral intake of Ge elixirs containing germanium dioxide (GeO2) or Ge-132. In these cases, biopsies show vacuolar degeneration in renal tubular epithelial cells, without proteinuria or hematuria, in the absence of glomerular changes. Serum creatinine levels have been well above 400 mumol/L in such patients. In 17 of 18 cases, accumulated elemental Ge intakes reportedly ranged between 16 to 328 g over a 4-36 mo period, or between 100 to 2000 times the average estimated dietary intake for human. In surviving patients, renal function improved after discontinuation of Ge supplementation. However, in no case was recovery complete. One organogermanium compound, an azaspiran organogermanium compound, 2-aza-8-germanspiro[4,5] decane-2-propamine-8,8-diethyl-N,N-dimethyl dichloride (spirogermanium), has been found to cause both neurotoxicity and pulmonary toxicity in phase I and II studies examining its chemotherapeutic potential as an antitumor drug in the treatment of various malignancies. In cancer patients given the drug spirogermanium, 40% experienced marked, yet transient neurotoxicity. Two patients suffered from pulmonary toxicity. Results of phases I and II human cancer trials for spirogermanium have not been favorable, with the exception of moderate benefits for three types of malignancies. It is recommended that patients exposed to long-term (greater than 3 mo) Ge supplementation at levels well above the estimated daily intake be medically supervised and monitored for potential renal-, pulmonary- or neurotoxicity. Further study regarding the mechanism of Ge-induced nephrotoxicity in human is warranted.

Effect of dietary iron deficiency on mineral levels in tissues of rats

Abstract: To clarify the influence of iron deficiency on mineral status, the following two synthetic diets were fed to male Wistar rats: a control diet containing 128 μg iron/g, and an iron-deficient diet containing 5.9 μg iron/g. The rats fed the iron-deficient diet showed pale red conjunctiva and less reactiveness than the rats fed the control diet. The hemoglobin concentration and hematocrit of the rats fed the irondeficient diet were markedly less than the rats fed the control diet. The changes of mineral concentrations observed in tissues of the rats fed the iron-deficient diet, as compared with the rats fed the control diet, are summarized as follows: • Iron concentrations in blood, brain, lung, heart, liver, spleen, kidney, testis, femoral muscle, and tibia decreased; • Calcium concentrations in blood and liver increased; calcium concentration in lung decreased; • Magnesium concentration in blood increased; • Copper concentrations in blood, liver, spleen and tibia increased; copper concentration in femoral muscle decreased; • Zinc concentration in blood decreased; • Manganese concentrations in brain, heart, kidney, testis, femoral muscle and tibia increased.

In vivo nephrotoxicity induced in mice by chromium(VI). Involvement of glutathione and chromium(V).

Abstract: The role of glutathione (GSH) and chromium (V) in chromium (VI)-induced nephrotoxicity in mice was investigated at 24 h after K2Cr(VI)2O7 ip injection. Nephrotoxicity was assessed by measurements of relative kidney weight and serum urea nitrogen. Cr(VI) nephrotoxicity was accompanied by decreased renal GSH and glutathione reductase (GSSG-R) levels. Pretreatment with buthionine sulfoximine, an inhibitor of GSH biosynthesis, enhanced Cr(VI)-induced nephrotoxicity, and remarkably diminished kidney GSH and GSSG-R levels. In contrast, pretreatment with glutathione methyl ester, a GSH-supplying agent, prevented Cr(VI) from exerting a harmful effect on mouse kidney and restored kidney GSH level. Administration of a Cr(V) compound, K3Cr(V)O8, induced much higher toxicity in mouse kidney than Cr(VI), but it failed to diminish renal GSH level. Another Cr(V) compound, Cr(V)-GSH complex, and Cr(III) nitrate did not cause a nephrotoxic effect in mice. The mechanism of Cr(VI)-induced nephrotoxicity was explained using GSH and Cr(V).

Dietary phytate × calcium/zinc millimolar ratios and zinc nutriture in some Ontario preschool children

Abstract: Millimolar ratios of phytate/Zn, Ca x phytate/Zn, and Ca x phytate/Zn per 4.2 MJ were calculated from 3-d weighed-food records collected from 62 male (M) (mean age: 58 +/- 7 mo [mean +/- SD]) and 44 female (F) (mean age: 58 +/- 6 mo) preschool children from Southern Ontario. Food-composition values for phytate were based on laboratory analysis and the literature. No gender differences existed for median millimolar ratios of phytate/Zn (median: M, 5.3; F, 5.3), and Ca x phytate/Zn per 4.2 MJ (M, 68.1; F, 59.5), but median intakes of phytate (M, 399; F, 333 mg/d) and median millimolar ratios of Ca x phytate/Zn (median: M, 102.1; F, 72.3; p less than 0.01) were higher for boys than for girls. Of the children, only two (1M, 1F) and 22 (17 M, 5F) had millimolar ratios of phytate/Zn and Ca x phytate/Zn per 4.2 MJ, respectively, that were above critical values. Millimolar ratios of Ca x phytate/Zn (p = 0.06) and Ca x phytate/Zn per 4.2 MJ (p = 0.05) were higher in boys with hair zinc less than 1.07 mumol/g v greater than or equal to 1.07 mumol/g. Analysis of variance showed that height was influenced by an interaction between millimolar ratios of Ca x phytate/Zn per 4.2 MJ and sex (p = 0.0007), when age and midparent height were treated as covariates. Results suggest that dietary Ca x phytate/Zn millimolar ratios, when expressed per 4.2 MJ, influenced the zinc nutriture of these Southern Ontario boys.

Metabolism, cellular actions, and cytotoxicity of selenomethionine in cultured cells.

Abstract: Selenomethionine metabolism and the biochemical basis for its cytotoxicity were analyzed in cultured human and murine lymphoid cells. The metabolic pathways were also addressed, using purified mammalian enzymes and crude tissue extracts. Selenomethionine was found to be effectively metabolized toS-adenosylmethionine analog, and that analog was further metabolized in transmethylation reactions and in polyamine synthesis, similarly to the corresponding sulphur metabolites of methionine. Selenomethionine did not block these pathways, nor was there a specific block on the synthesis of DNA, RNA, or proteins when added to the culture medium. Selenomethionine showed cytotoxicity at above 40 μM levels. Yet, low selenomethionine levels (10 μM) could replace methionine and support cell growth in the absence of methionine. Selenomethionine toxicity took place concomitantly with changes inS-adenosylmethionine pools. D-form was less cytotoxic than L-form. Methionine concentration modified the cytotoxicity. Together, this indicates that selenomethionine uptake and enzymic metabolism are involved in the cytotoxicity in a yet unknown way.

Effect of an acute zinc depletion on rat lipoprotein distribution and peroxidation

Abstract: The aim of this study was to determine the extent to which zinc depletion leads to lipoprotein modifications by measuring both lipoprotein-fraction distribution and peroxidation in zinc-depleted rats The animals were divided into three groups and fed for 8 wk a zinc-adequate diet (100 ppm) ad libitum (AL), a zinc-deficient diet (02 ppm) ad libitum (ZD), or a zinc-adequate diet according to the pair feeding method (PF) Trace-element status, tissular lipids, and lipoprotein-fraction study were performed The MDA production by the lipoprotein fraction was measured before and after induced peroxidation Cholesterol and phospholipids were increased in ZD rats An important increase of VLDL and IDL was observed and a significant enhanced production of MDA by the LDL was related to zinc deficiency From this observation, we may conclude that LDL fractions of ZD rats are more susceptible to induced oxidative damage These results suggest that in zinc deficiency, the lipoprotein fragility is an aggravating factor of peroxidation and the dyslipoproteinemia may lead to an atherogenic risk

Serum zinc and copper in myocardial infarction with particular reference to prognosis.

Abstract: Serum copper and zinc estimations in humans were made to find their diagnostic and prognostic value in cases of myocardial infarction. Following infarction, there was an increase in serum copper levels from the first 24 h up to the 7th day, with gradual decline that did not reach the normal value up to the 14th day. The serum zinc levels declined in the first 24 h until the 4th day and increased to the normal value on the 14th day. It is concluded that, for diagnosis of myocardial infarction, serum zinc levels are more useful during the first week and copper levels in the second week after the onset of infarction.

Reevaluation of a sensitive indicator of early lead exposure. Measurement of porphobilinogen synthase in blood.

Abstract: A principal target for the environmental toxin lead (Pb) is porphobilinogen synthase (PBGS), a Zn-metalloenzyme necessary for heme biosynthesis. Measurement of blood Pb inhibited PBGS is the most sensitive indicator of subclinical Pb intoxication, but problems with the assay have diminished its use. This report identifies Pb as a slow acting inhibitor of PBGS. The activity of PBGS could change up to sixfold during an hourlong clinical assay of Pb contaminated blood, and activity is profoundly effected by the presence of serum proteins, such as albumin. When PBGS catalyzed PBG production is allowed to reach a steady state rate, kinetic data on purified PBGS support the hypothesis that Pb inhibition of PBGS results from direct substitution for Zn.

Influence of nicotine on tissue trace element concentrations and tissue antioxidant defense.

Abstract: Both altered trace element metabolism and cigaret smoking have been proposed to be risk factors for cardiovascular disease (CVD). Thus, it is important to identify the mechanisms by which cigaret smoke alters trace element metabolism. In the present study, serum trace element concentrations were measured in 19 smokers and 13 nonsmokers. In parallel studies, data from rats treated with 50 mg of nicotine over a 21-d period tested the hypothesis that nicotine induced altered trace element metabolism observed in smokers. Serum Cu and Zn concentrations were significantly higher in smokers than in nonsmokers. Serum nicotine concentrations in rats were comparable to those observed in heavy smokers, but serum trace element concentrations were not significantly altered by nicotine treatment. Tissue trace element concentrations were also not markedly affected by nicotine; however, trace element ratios in liver, kidney, lung, and brain were significantly altered by nicotine treatment. In addition, nicotine-treatment resulted in significantly lower liver glutathione concentrations and higher Cu, Zn superoxide dismutase activity than in controls. These data show that a 50-mg infusion of nicotine over 21 d does not produce in rats the serum trace element abnormalities observed in cigaret smokers. However, nicotine did affect the trace element relationships between tissues as well as components of the free radical defense system.

Effect of selenium compounds and thiols on human mammary tumor cells

Abstract: The effect on cell viability and growth rate of sodium selenite, selenocystine, sodium selenate, and selenomethionine at selenium concentrations of 6.25 and 12.5 uM was studied in vitro on cells of the human mammary tumor cell line HTB123/DU4475. Selenite and selenocystine affected both cell viability and growth rate of the tumor cells at these selenium concentrations. Selenite and selenocystine decreased intracellular glutathione concentrations, but did not affect tumor cell glutathione peroxidase activity. After six days of exposure to either selenate or selenomethionine, the viability of tumor cells remained stable, but cell growth, as measured by numbers of cells, was retarded. Neither selenate nor selenomethionine produced changes in concentrations of intracellular glutathione. The toxic effect of selenite on tumor cells was enhanced by addition of 0.25 mM glutathione to the growth medium. Preincubation of the tumor cells with 62.5 uM buthionine sulfoximine decreased cellular glutathione to 15% of controls at 24 h and enhanced the toxicity of selenite toward the tumor cells. Glutathione, 2-mercaptoethanol, andl-cysteine were all toxic to the tumor cells in a dose-dependent manner.

Developmental toxicity evaluation of orthovanadate in the mouse

Abstract: Sodium orthovanadate in deionized water was administered once daily by gavage on gestational days 6-15 to mice at doses of 0, 7.5, 15, 30, and 60 mg/kg. Dams were killed on day 18 of pregnancy, and fetuses were examined for external, visceral, and skeletal defects. Maternal toxicity was observed at the highest doses of sodium orthovanadate, as evidenced by a significant number of deaths (60 and 30 mg/kg/d) and reduced weight gain and food consumption (30 and 15 mg/kg/d). Embryolethality and teratogenicity were not observed at maternally toxic doses and below, but fetal toxicity was evidenced by a significant delay in the ossification process of some skeletal districts at 30 mg/kg/d. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 7.5 mg/kg/d, and 15 mg/kg/d represented a NOAEL for developmental toxicity in mice under the conditions of this study.

Factors affecting the determination of total mercury in biological samples by continuous-flow cold vapor atomic absorption spectrophotometry

Abstract: The acidic reduction of Hg using a continuous-flow analytical system was evaluated. With 25% SnCl2 as the reductant, characteristic concentrations (sensitivities) of 0.44 microgram/L (open cell) and 0.29 microgram/L (flow-through cell) were obtained using inorganic Hg2+ standards in 1.5% HCl. When CH3Hg+ standards were used, absorption signals were an order of magnitude lower, indicating that Sn(II) is incapable of producing Hg degree from organic Hg in this acidic reduction system. Addition of CdCl2 to the SnCl2 reductant, as suggested by Magos (1) for the reduction of organomercurials under alkaline conditions, was without beneficial effect. Similarly, combining Sn with another reducing agent (hydroxylamine hydrochloride), or a strong alkaline solution (40% NaOH), in the reaction coil of the flow-through system did not significantly enhance the Hg absorption signal for either inorganic or organic Hg. Recovery of Hg from spiked liver homogenates digested at 70-80 degrees C using a HNO3/H2SO4/HCl procedure and stabilized with 0.5 mM K2Cr2O7 was > 85% using either inorganic Hg2+ or CH3Hg+, indicating that this digestion procedure successfully breaks the C-Hg bond to form readily reducible Hg species. Using L-cysteine to stabilize standards of inorganic Hg2+ in HCl caused significant depressions of the Hg absorption signal at L-cysteine concentrations > 0.001% (approximately 0.5 mM); 0.1% L-cysteine caused total suppression of the Hg signal. These results indicate that: (1) acidic reduction of Hg by Sn in this continuous-flow system requires breakdown of organomercurials prior to analysis; (2) tissue digestion using HNO3/H2SO4/HCl followed by the addition of K2Cr2O7 to stabilize Hg2+ achieves this breakdown and allows good recovery of total Hg; and (3) use of L-cysteine to complex and prevent losses of Hg should be avoided in systems using acidic reduction of Hg. Concentrations of endogenous tissue sulfhydryls are generally lower than those associated with depressed absorbance signals during the acidic reduction of Hg.

The distribution and half-life for retention of vanadium in the organs of normal and diabetic rats orally fed vanadium(IV) and vanadium(V).

Abstract: The concentration of vanadium in organs of diabetic rats that had been fed vanadium, either as V(IV) or V(V), in their drinking water has been determined. The kidney was found to have the highest concentration, about 185 nmol/g wet tissue. This averages about three times higher than for the liver or spleen, for which concentrations were comparable. The lung, blood plasma, and blood cells tended to have the lowest accumulations of vanadium. A time-course study indicated that the half-life for elimination of vanadium from the bodies of vanadium-fed rats is about 12 d.

Changes in element concentration and distribution in breast-milk fractions of a healthy lactating mother.

Abstract: Daily changes in components of breast milk with number of days of lactation after delivery were demonstrated by determining concentrations and distributions of several elements simultaneously. Concentrations of calcium, copper, magnesium, phosphorus, sulfur, and zinc were determined simultaneously by inductively coupled argon plasma-atomic-emission spectrometry (ICP) for whole milk and milk fractions (skimmed milk and whey) collected from 2 to 196 d postpartum from a healthy lactating mother. Calcium and phosphorus concentrations increased in transitional milk. With days postpartum, the other elements decreased from the highest concentrations in colostrum milk, the modes of decrease being characteristic for each element. Distributions of copper, iron, phosphorus, sulfur, and zinc in whey were determined on a gel-filtration column by HPLC with ICP detection (HPLC-ICP method). Distributions of the five elements and absorbance peaks at 254 and 280 nm changed dramatically day by day at the beginning (colostrum milk), resulting in constant distributions after 30 d (mature milk). These results suggest the important roles of daily changing constituents in breast milk, especially in colostrum milk, in the nutrition of the newborn. Several element peaks on a gel-filtration column were identified by comparison with standard samples.

Combined exposure to lead and ethanol on tissue concentration of essential metals and some biochemical indices in rat.

Abstract: The effect of daily oral administration of ethanol (2.5, 5, or 10% in drinking water for 8 wk), lead (10 mg/kg, po, once daily for 8 wk), or their combination on tissue trace-metal concentration and hematopoietic and hepatic biochemical indices was investigated in male rats. Ethanol (10%) ingestion enhanced the hepatic lipid peroxidation and decreased the calcium and magnesium content of blood and liver. Coexposure to lead and ethanol (5 and 10%) produced a more pronounced elevation of blood zinc protoporphyrin (ZPP) and hepatic lipid peroxidation. Combined lead-ethanol exposure also lowered the concentration of blood and hepatic magnesium and calcium and increased the amount of lead in the blood, liver, and brain compared to a group treated with lead alone. The results suggest that chronic alcohol ingestion results in calcium and magnesium loss. However, coexposure to lead and ethanol could result in more serious depletion of calcium and magnesium, and this could be the cause of suspected synergism between alcohol consumption and lead poisoning.

Zinc deficiency, ethanol, and myocardial ischemia affect lipoperoxidation in rats.

Abstract: The production of oxygen free radicals can be stimulated by excess iron, cadmium, nickel, and the like. Inversely, copper, zinc, and selenium inhibit production, either via their own action or via antiradical metalloenzymes. The study involved determining the effect of zinc deficiency combined with chronic ethanol administration on the status of blood and tissue free radicals, as well as on cardiac function in isolated perfused rats' hearts. Animals were fed a basic diet containing residual zinc at 0.2–0.3 ppm. Following a zinc deficiency lasting 5 wk, which during the last 4 wk was accompanied by chronic ethanol administration, hearts were submitted to ischemia for 30 min in vitro, followed by reperfusion. Biochemical analyses (zinc, superoxide dismutase, malondialdehyde, conjugated dienes, and so on) were performed in the blood and in the homogenates of different organs.

Dietary calcium and blood lead levels in women.

Abstract: Nutritional factors are known to influence metabolism and toxicity of several metals in animal experiments, but relevant human data are scarce and inconclusive. In this work, we tested the hypothesis that dietary calcium influences lead metabolism in humans. Blood lead concentrations were used as indicators of lead exposure and metabolism. Two groups of peasant women living in similar conditions in two different regions in Yugoslavia (100 in each) were chosen as subjects for this purpose. In region A, the dietary calcium intake was about 940 mg, and in region B about two times lower, i.e., 450 mg/day. The average blood lead concentration was significantly lower in women from region A (69 micrograms/L) than from region B (83 micrograms/L). Our results support the assumption that adequate calcium intake might be one of the preventive measures for decreasing lead absorption. This new evidence, sought for some time by nutritionists and toxicologists, needs further international confirmation.

Detection of two Zn-finger proteins of Xenopus laevis, TFIIIA, and p43, by probing western blots of ovary cytosol with 65Zn2+, 63Ni2+, or 109Cd2+.

Abstract: Tow Zn-finger proteins, TFIIIA (a constituent of 7S RNP particles) and p43 (a constituent of 42S RNP particles), were detected in ovary extracts of juvenileXenopus laevis females by in vitro binding of radiolabeled divalent metals. Proteins fractionated by SDS-PAGE (sodium dodecylsulfate-polyacrylamide gel electrophoresis) were transferred by Western blotting onto nitrocellulose membranes, probed with65Zn2+,63Ni2+, or109Cd2+, and visualized by autoradiography. Detection limits for TFIIIA were approx 0.07 μg/well by109Cd2+-probing, 0.13 μg/well by65Zn2+-probing, and 0.26 μ/well by63Ni2+-probing. Protein p43 was more clearly visualized by probing with63Ni2+ than with65Zn2+ or109Cd2+. After purified TFIIIA was cleaved with cyanogen bromide,65Zn2+,109Cd2+, and63Ni2+ distinctly labeled the 22 kDa middle fragment;65Zn2+ and109Cd2+ also labeled the 11 kDa N-terminal fragment, but didnot label the 13 kDa C-terminal fragment. These results are consistent with the notion that the radioligands were bound to finger-loop domains of TFIIIA, which occur in the middle and N-terminal fragments. Based on the abilities of nonradioactive metal ions to compete with65Zn2+ for binding to TFIIIA on Western blots, the relative affinities of the metals for TFIIIA were ranked as follows: Zn2+=Cu2+≥Hg2+>Cd2+>Co2+≥Ni2+. Even at a 1000-fold molar excess, Mn2+ did not compete with65Zn2+ for binding to TFIIIA. Probing Western blots with the radiolabeled metal ions greatly facilitates the detection, isolation, and quantitation of TFIIIA and p43.

Teratogenicity of Ni2+ in Xenopus laevis, assayed by the FETAX procedure.

Abstract: The teratogenicity of Ni2+ was tested by the FETAX (Frog Embryo Teratogenesis Assay:Xenopus) procedure in the South African frog,Xenopus laevis. In seven assays, beginning at 5 h postfertilization, groups ofXenopus embryos were incubated for 96 h in media that contained Ni2+ (added as NiCl2) at concentrations ranging from 1 × 10−7 to 3 × 10−3 mol/L; control groups were incubated in the same medium without added NiCl2. At 101 h postfertilization, surviving embryos were counted, fixed in formalin, and examined by microscopy to determine their developmental stages, malformations, and head-to-tail lengths. In control embryos, survival was ≥95% and malformations were ≤7%. Malformations were found in >95% of embryos exposed to Ni2+ concentrations ≥5.6 μmol/L. The most frequent malformations in Ni2+-exposed embryos were ocular, skele|tal, and intestinal deformities; less common malformations included facial, cardiac, and integumentary deformities. Other abnormalities, not categorized as malformations, included stunted growth, dermal hypopigmentation, and coelomic effusions or hemorrhages. Themedian embryolethal concentration (LC50) of Ni2+ was 365 (SE±9) μmol/L; themedian teratogenic concentration (EC50) was 2.5 (SE±0.1) μmol/L; theTeratogenic Index (TI=LC50/EC50) was 147 (SE±5), indicating that Ni2+-exposures were limited to specific 24 h periods showed thatXenopus embryos were most susceptible to Ni2+-induced malformations on the second and third days of life, during the most active period of organogenesis.

Maternal hair zinc concentration in neural tube defects in Turkey

Abstract: Hair zinc concentration was measured in samples taken from 57 mothers who delivered infants with neural tube defects (NTD) (mainly anencephaly). Control groups consisted of 30 healthy mothers with normal offspring and 37 nonpregnant women from middle-income backgrounds. Zinc concentration was also measured in the hair of eight infants with NTD (four being anencephalic). The mean maternal hair zinc concentration in the NTD group (128.2±38.9 μg/g) was lower than that of the control women (p<0.001), whereas the mean hair zinc level of malformed babies (250.4±85.2 μg/g) was significantly higher than that of normal infants (193.4±39.2 μg/g) (p<0.05). Maternal nutritional zinc deficiency was thought to be one of the factors responsible for NTD in Turkey.

The effect of various dietary zinc concentrations on the biological interactions of zinc, copper, and iron in rats

Abstract: Three groups (14 rats each) were fed one of the following diets for 8 wks: a control purified basal diet containing 12 ppm zinc, 5 ppm copper, and 35 ppm iron; the basal diet with <2 ppm zinc; or the basal diet supplemented with 1000 ppm zinc. Rats fed the zinc-deficient diet had decreased weight gain, moderate polydipsia, and intermittent mild diarrhea. The zinc-supplemented rats had a cyclical pattern of food intake and weight loss from weeks 5 to 8. Tissue concentrations suggest that zinc and copper were not mutually antagonistic with chronic dietary imbalances. If tissue element concentrations reflected intestinal uptake, then competition and/or inhibition of intestinal uptake occurred between zinc and iron. The fluctuations in tissue element concentrations that occurred with increased duration of the study were at variance with previous studies of shorter time periods. The dietary proportions of zinc, copper, and iron appear to influence zinc, copper, and iron metabolism at the intestinal and cellular transport levels over a given period of time.

Parenteral supplementation with zinc in surgical patients corrects postoperative serum-zinc drop.

Abstract: Zinc has been known for a long time to facilitate wound healing. But, so far, supplementation trials in patients treated by major severity surgery gave either partial or controversial results. In a double-blind, randomized study including 30 patients, we show that zinc supplements (30 mg/d for 3 d) administered by a drip correct postoperative drop of serum zinc, that this correction concerns the available part of serum zinc (i.e., zinc that is bound to compounds other than alpha-2 macroglobulin in serum), and that this supplementation can improve clinical wound healing. Possible influence of increased urinary output after the intervention is discussed, and we found that serum cortisol remains stable when zinc/albumin ratio is stable, and increases sharply when the same ratio drops. Cortisol, therefore, seems to play a major role in zinc redistribution after surgery.

Products of the reaction of selenite with intracellular sulfhydryl compounds

Abstract: The usual first step in the intracellular metabolism of exogenous selenite is its chemical reaction with glutathione to form selenodiglutathione (1). We have investigated whether selenite also reacts intracellularly with other SH compounds. HeLa cells were exposed to [75Se]selenite and lysed with SDS. Cellular proteins and nucleic acids were precipitated with trichloroacetic acid, and the acid-soluble fraction was analyzed by ion-exchange thin-layer chromatography (ion-exchange TLC) and autoradiography. In control cells, the major [75Se]-containing species detected can be identified by its mobility as selenodiglutathione. Two other species were detected, which can be identified as selenodimercaptoethylamine and the mixed selenotrisulfide of mercaptoethylamine and glutathione. In contrast, in cells that were depleted of glutathione (by treatment with buthionine sulfoximine), very little, if any, selenodiglutathione was detected. However, new [75Se]-containing species were detected, which can be identified as selenodicysteine and the mixed selenotrisulfide of cysteine and glutathione. The same species were detected when [75Se]selenite was added to the acid-soluble fraction of a cell extract (as opposed to living cells), confirming that these compounds can be formed by nonenzymatic reactions.

Selenium and Behçet's disease.

Abstract: Behcet's disease is an inflammatory disorder of unknown etiology, characterized by recurrent oral and genital aphthous ulcers, ocular inflammation, and skin lesions of erythema nodusum and acneiformeruptions. Selenium (Se) affects all components of the immune system, i.e., the development and expression of nonspecific, humoral, and cell-mediated responses. In general, a deficiency in Se appears to result in immunosuppression, whereas supplementation with low doses of Se appears to result in augmentation and/or restoration of immunoglogic functions. In this study, the distribution of Se and IgG, IgM in serum were compared in samples from healthy adult control and Behcet's disease patients. The serum Se levels were measured by AA-30-40 Varian Spectra, and immunoglobulins were measured by immunodiffusion technique. The mean (SD) serum Se level of 54.24 ± 8.06 ng/mL among Behcet's disease subjects was significantly different (P<0.01) from that in the control subjects (90.01 ± 9.94 ng/mL). We also measured IgG and IgM as 10.01 ± 2.74 mg/mL and 1.26 ± 0.29 mg/mL, respectively for patients, and 15.08 ± 4.73 mg/mL and 1.58 ± 0.43 mg/mL for controls. The mean values of IgG and IgM for patients were significantly (P<0.05) different from the values of controls. It seems, therefore, that a deficiency in selenium impedes the humoral immune response.

Trace elements in human transitory milk. Variation caused by biological attributes of mother and infant.

Abstract: Multielement analysis was performed on human milk collected on 5-9-d postpartum from 51 Japanese females using inductively coupled plasma (ICP) mass spectrometry (MS), ICP atomic emission spectrometry (ICP-AES) and fluorometry. Thirty-one elements were detected by these analytical methods in milk. Twelve elements (Na, Mg, P, S, K, Ca, Cu, Zn, Se, Sr, Rb, and Mo) were detected in all of the samples. Al, Cs, and Ba were the elements detected by ICP-MS in more than half of the samples. Multiple regression analysis extracted biological attributes of mother and infant, such as maternal stature, maternal wt, or infant's birth wt, as statistically significant factors contributing to the variation in elemental concentration in milk. However, the rates of contribution were small in all cases. It was concluded that the biological attributes of mother and infant examined in this study were not the major factors that contribute to elemental variation in human milk.