The effect of pregnancy on renal clearance of boron in humans: a study based on normal dietary intake of boron.
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Boron occurs most frequently in nature as borates and boric acid, never as the free element. Its largest uses are in glass, detergents, and agriculture. Essential for higher plants, there is growing evidence for essentiality in vertebrates. Humans consume daily about a milligram of boron, mostly from fruit and vegetables. At high doses, boron is a developmental and reproductive toxin in animals. Pregnant rats were the most sensitive. An oral NOAEL of 9.6 mg B/kg/day was established for developmental toxicity in Sprague-Dawley rats fed boric acid. To extrapolate from the large, animal boron toxicity database to humans, especially to pregnant women, information on renal clearance of boron was needed. This study's purpose was to measure renal clearance of boron in pregnant and nonpregnant woman. In 16 second trimester women and 15 nonpregnant age-matched referents, dietary boron provided the blood and urine boron concentrations used for calculating boron clearance. The pregnant and nonpregnant boron intake was 1.35 and 1.31 mg boron/24 h, respectively. Blood for boron, creatinine, and urea was collected at the start, at 2 h, and at 24 h. Urine was collected during the first 2 h in the Clinical Research Center and during a 22-h period outside the center for measurement of volume, boron, and creatinine. Renal boron clearance measured over the initial 2 h, the most complete urine collection period, was 68.30ml/min/1.73 m(2) for pregnant subjects and 54.31ml/min/1.73 m(2) for nonpregnant subjects. Comparison of renal boron clearance with creatinine clearance indicated that tubular reabsorption of boron occurred in both pregnant and nonpregnant women. (+info)
The effect of pregnancy on renal clearance of boron in rats given boric acid orally.
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Boric acid (H(3)BO(3)) has been shown to cause developmental abnormalities in the offspring of pregnant rats. Comparative data on the renal clearance of boron (B) in rats and humans, both pregnant and nonpregnant, exposed to boric acid (BA) would reduce uncertainty in interspecies extrapolation from rats to humans. The purpose of this study was to evaluate the effect of pregnancy on the plasma half-life and renal clearance of boron in Sprague-Dawley rats given a single oral dose of boric acid. For the half-life study, nonpregnant and pregnant (gestation day 16) rats were given a single dose of 30 mg/kg of boric acid by gavage, and plasma samples were collected at 2-3 h intervals. The plasma half-life of boron was determined to be 2.9 +/- 0.2 and 3.2 +/- 0.3 h in nonpregnant and pregnant rats, respectively. In the clearance study, nonpregnant and pregnant (GD 16) rats were given a single gavage dose of 0.3, 3, or 30 mg/kg of boric acid. Boron clearance was slightly higher in pregnant rats (3.3 +/- 0.6, 3.2 +/- 0.5, and 3.4 +/- 0.5 ml/min/kg, respectively) compared to nonpregnant rats (3.1 +/- 0.8, 3.0 +/- 0.6, and 3.2 +/- 0.5 ml/min/kg, respectively), but the difference was not statistically significant and not dose-related. Boron clearance was less than creatinine clearance, suggesting tubular reabsorption in both groups. In conclusion, pregnancy did not appear to significantly alter the renal clearance or the plasma half-life of boron in Sprague-Dawley rats under the conditions of this study. (+info)
Applications of mechanistic data in risk assessment: the past, present, and future.
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Mechanistic data, when available, have long been considered in risk assessment, such as in the development of the nitrate RfD based on effects in a sensitive group (infants). Recent advances in biology and risk assessment methods have led to a tremendous increase in the use of mechanistic data in risk assessment. Toxicokinetic data can improve extrapolation from animals to humans and characterization of human variability. This is done by the development of improved tissue dosimetry, by the use of uncertainty factors based on chemical-specific data, and in the development of physiologically based pharmacokinetic (PBPK) models. The development of the boron RfD illustrates the use of chemical-specific data in the improved choice of uncertainty factors. The draft cancer guidelines of the U.S. Environmental Protection Agency emphasize the use of mode of action data. The first choice under the guidelines is to use a chemical-specific, biologically based dose-response (BBDR) model. In the absence of a BBDR model, mode of action data are used to determine whether low-dose extrapolation is done using a linear or nonlinear (margin of exposure) approach. Considerations involved in evaluating a hypothesized mode of action are illustrated using 1,3-dichloropropene, and use of a BBDR model is illustrated using formaldehyde. Recent developments in molecular biology, including transgenic animals, microarrays, and the characterization of genetic polymorphisms, have significant potential for improving risk assessments, although further methods development is needed. Overall, use of mechanistic data has significant potential for reducing the uncertainty in assessments, while at the same time highlighting the areas of uncertainty. (+info)
Lectin-like glycoprotein PsNLEC-1 is not correctly glycosylated and targeted in boron-deficient pea nodules.
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Symbiosome development was studied in pea root nodules from plants growing in the absence of boron (B). Rhizobia released into the host cells of nodules from B-deficient plants developed to abnormal endophytic forms with an altered electrophoretic lipopolysaccharide pattern. Immunostaining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting of nodule homogenates with antibodies that recognize glycoprotein components showed that two previously described lectin-like glycoproteins (PsNLEC-1A and PsNLEC-1B) did not harbor the carbohydrate epitope normally recognized by specific monoclonal antibodies. Material derived from B-deficient nodules, however, still contained three antigenic isoforms with similar electrophoretic mobilities to PsNLEC-1 isoforms A, B, and C. These could be detected following immunoblotting and immunostaining with a specific antiserum originating from the purified PsNLEC protein that had been heterologously expressed in Escherichia coli. Immunogold localization of PsNLEC-1 sugar epitopes in B-deficient nodules showed that they were associated mostly with cytoplasmic vesicles rather than normal localization in the symbiosome compartment of mature infected cells. These results suggest that a modification of the glycosyl-moieties of PsNLEC-1 and an alteration of vesicle targeting occur during the development of pea nodules in the absence of B, and that these changes are associated with the development of aberrant nonfunctional symbiosomes. (+info)
Diadenosine phosphates and S-adenosylmethionine: novel boron binding biomolecules detected by capillary electrophoresis.
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There is evidence that boron has a physiological role in animals and humans, but the search for boron binding biomolecules has been difficult because useful radioactive boron isotopes do not exist. To overcome this limitation we used capillary electrophoresis to identify and quantify boron binding to biomolecules by detecting the negative charge boron imparts to ligands. The effect of molecular structure and proximal electronic charges of adenosine and molecules with adenosine moieties including S-adenosylmethionine (SAM) and diadenosine polyphosphates (Ap(n)A) were compared. The boron affinity of the test species varied with the rank order SAM congruent with Ap(6)A congruent with Ap(5)A>Ap(4)A>Ap(3)A congruent with NAD(+)>Ap(2)A>NADH congruent with 5'ATP>5'ADP>5'AMP>adenosine>3'AMP congruent with 2'AMP congruent with cAMP congruent with adenine. Test species with vicinal cis-diols bound boron; species without those moieties did not. Boron binding affinity increased when proximal cationic moieties were present. Anionic moieties remote from the cis-hydroxyl binding site also positively influenced boron binding affinity. In the Ap(n)A species, cooperative complexing of boron between the terminal ribose moieties apparently occurred. In these species boron affinity greater than expected for two monocomplexes was observed and binding affinities increased as more phosphate groups (beyond three) were present separating the terminal moieties. Our results indicate that Ap(6)A, Ap(5)A, Ap(4)A, Ap(3)A, and SAM have higher affinities for boron than any other currently recognized boron ligand present in animal tissues including NAD(+). (+info)
Inflammatory response, growth, and thyroid hormone concentrations are affected by long-term boron supplementation in gilts.
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An experiment was conducted to determine the long-term effects of dietary boron (B) on growth performance, immune function, and plasma and serum characteristics in gilts. Fifty weanling gilts were allotted to 10 pens based on weaning weight and litter origin. Pens were randomly assigned to receive one of two dietary treatments. Treatments consisted of a basal diet low in B (control) and the basal diet supplemented with 5 mg B/kg diet as sodium borate. Gilts remained on their respective experimental diets and with their penmates throughout the nursery, growing, and finishing phases. The B concentration of the basal diet was 0.98, 2.1, and 2.2 mg/kg diet during the nursery, growing, and finishing phases, respectively. At the end of each production phase, animals were weighed and feed consumption was determined to assess growth performance variables. In addition, blood samples were obtained from three randomly selected gilts per pen at the completion of each phase. Boron had no affect (P > 0.58) on growth performance during the nursery phase, but gilts receiving supplemental B had increased (P < 0.05) ADG at the end of the finishing phase and over the entire growing-finishing period. Serum concentrations of triiodothyronine (T3) tended (P < 0.07) to be reduced by dietary B at the end of the nursery phase, but serum thyroxine (T4) was not affected (P = 0.46) by B. At the completion of the growing phase, supplemental B decreased (P < 0.05) the concentrations of T3 and T4 in the serum. In addition, serum concentrations of total cholesterol and the activity of alkaline phosphatase were increased (P < 0.05) by dietary B at the end of the growing phase. Serum concentrations of urea N tended (P < 0.09) to be increased by B at the end of the growing phase. Beginning at d 95 of the experimental period, measures of immune function were assessed in randomly selected gilts. Boron decreased (P < 0.05) the inflammatory response to an intradermal injection of phytohemagglutinin. Boron did not affect (P > 0.30) the blastogenic response of isolated lymphocytes to mitogen stimulation or the humoral immune response against a sheep red blood cell suspension. Results indicate that B may affect serum thyroid hormone concentrations, the inflammatory response, and growth in pigs. (+info)
Boron supply into wheat (Triticum aestivum L. cv. Wilgoyne) ears whilst still enclosed within leaf sheaths.
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The present study investigates whether there is significant remobilization of (10)B previously loaded in the flag and penultimate leaves into the young, actively growing ear enclosed within the sheaths of flag and penultimate leaves. It also explores whether B transport into the enclosed ear declines when air humidity in the shoot canopy increases. After 5 d (10)B labelling during the period from early to full emergence of the flag leaf, the plants were transferred into nutrient solutions containing either 10 microM (11)B or no added B for 3 d. Regardless of the subsequent B supply levels to the roots, (10)B contents in the ear continued to increase by up to 5-fold 3 d after the end of (10)B supply in the nutrient solution. During these 3 d, the ear experienced a rapid increase in biomass. However, the majority of B in the ear during the 3 d treatment period was from the newly acquired (11)B from root uptake, rather than retranslocation of (10)B previously deposited in the leaves. By comparing the relative distribution of (10)B, Rb (xylem-to-phloem transfer marker) and Sr (xylem-marker) in the ear and the flag leaf, the distribution of (10)B resembled that of Rb more than Sr. Canopy cover treatment greatly suppressed leaf transpiration and decreased the amount of newly acquired (10)B in the flag leaf and the ear, but not in the upper stem segments. The results suggest that whilst the young ear was still fully enclosed within the leaf sheaths without any significant transpiration activity, B transport into the ear is predominantly dependent on the long-distance B transport in the xylem driven by leaf transpiration and, therefore, on concurrent B uptake from the roots. (+info)
Formation of rhamnogalacturonan II-borate dimer in pectin determines cell wall thickness of pumpkin tissue.
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Boron (B) deficiency results in inhibition of pumpkin (Cucurbia moschata Duchesne) growth that is accompanied by swelling of the cell walls. Monomeric rhamnogalacturonan II (mRG-II) accounted for 80% to 90% of the total RG-II in B-deficient walls, whereas the borate ester cross-linked RG-II dimer (dRG-II-B) accounted for more than 80% of the RG-II in control plants. The results of glycosyl residue and glycosyl linkage composition analyses of the RG-II from control and B-deficient plants were similar. Thus, B deficiency does not alter the primary structure of RG-II. The addition of (10)B-enriched boric acid to B-deficient plants resulted within 5 h in the conversion of mRG-II to dRG-II-(10)B. The wall thickness of the (10)B-treated plants and control plants was similar. The formation and possible functions of a borate ester cross-linked RG-II in the cell walls are discussed. (+info)