LEAD-X Oral Solution, EDTA and Lead Interact to Fetal and Neonatal Growth in Rats during Pregnancy and Lactation
Department of China Program, William Penn University, Oskaloosa, IA.US
力德希口服液、EDTA和铅对孕期和哺乳期子鼠生长发育的影响
(论文简述)
ETCZRLEAD-X Oral Solution is provided as the source of Crude polysaccharide, Zinc, Selenium and Vitamins, a form widely used in lead poisoning prevention. We studied the effects of Basic , LEAD-X and EDTA diet to fetal and neonatal growth, lead levels, erythropoiesis and blood pressure in rats during pregnancy and lactation. Pregnant SD rats (n = 49) were randomly assigned to one of 6 groups of 8~9 rats each. Half of the rats were fed diets of basic diet, LEAD-X diet and EDTA diet, and exposed to 250mg/L of lead in their drinking water for the duration of the pregnancy and for 1wk of lactation. Three control groups were fed the same diets without lead exposure. Pups were studied at 1d and 1wk of age. Maternal and fetal blood and organ samples from the groups fed the basic diet had the highest lead concentrations, whereas the lowest lead concentrations were found in the groups fed LEAD-X diet and EDTA diet. Dam and pup hemoglobin concentrations, hematocrits, and body weights and lengths were reduced by lead exposure and EDTA. Dam systolic blood pressures during the third trimester of gestation were significantly higher in rats exposed to lead and fed the basic diet than in rats in the other five treatment groups. The results demonstrate that LEAD-X, EDTA and lead exposure interact in rats to influence maternal blood pressure, erythropoiesis, and fetal and neonatal growth during pregnancy and lactation. LEAD-X is safety and effective in preventing lead poisoning, will protect the mother fetus and neonate from lead accumulation and toxicity.
力德希口服液富含多种植物多糖和锌、硒等多种微量元素和维生素，是专门用于铅损伤防治和强身健体的保健食品。我们研究了基础膳食、力德希膳食和EDTA膳食对孕期和哺乳期铅暴露胎鼠和幼鼠生长发育、原卟啉和血压的影响。将受孕SD大鼠49只随机分为6组,每组8-9只。在孕期和产后1周的哺乳期内，将大鼠分为二部分，一部分（3组）作为实验组，在给予250mg/L的醋酸铅饮水的同时分别给予基础膳食、力德希膳食和EDTA膳食；另一部分（3组）作为对照组在给予洁净饮水的同时分别给予基础膳食、力德希膳食和EDTA膳食。在产后第一天和一周对子鼠进行研究，结果发现，基础膳食组母鼠和子鼠脏器和血液中铅的浓度最高，相反，力德希组和EDTA组母鼠和子鼠脏器和血液中铅的浓度最低。铅暴露和EDTA干预均可使胎鼠和子鼠的血红蛋白浓度、红细胞容积、体重和身长减低。在孕期的三个生长期，铅暴露合并基础膳食组大鼠的收缩压较其他五组的均有所升高。试验证明，在孕期和哺乳期，力德希口服液、EDTA和铅暴露对母鼠的原卟啉、血压以及胎鼠和幼鼠的生长发育均有影响，力德希口服液可安全有效地防治铅损伤,保护母婴远离铅蓄积和铅毒害。
Crude polysaccharide, Zinc, Selenium, Iron and vitamins, a form widely used in lead poisoning prevention. Diets low in crude polysaccharide, Zinc, Selenium, Iron and vitamins may increase the gastrointestinal absorption and toxicity of lead. Increasing dietary polysaccharide, Zinc, Selenium, Iron and vitamins during pregnancy could reduce lead toxicity, and might simultaneously increase vitamins and minerals absorption and erythropoiesis. Crude polysaccharide, vitamins and minerals requirements are higher during pregnancy. In addition, the ability of vitamins and minerals to reduce lead toxicity could be impaired by the enhanced lead absorption that occurs during pregnancy, and by pregnancy-induced changes in calcium homeostasis, as well as by EDTA. The latter also reduced organ iron and calcium concentrations and prevented lead-induced increases in free erythrocyte protoporphyrin.
The fetus and neonate are especially sensitive to toxic effects of lead. It has been estimated that more than 400,000 pregnant women annually ill the United States have blood lead concentrations in excess of 0.5 μmol/L, a level that may have adverse effects on the fetus. Thus, dietary factors that may modify fetal lead toxicity during pregnancy and lactation could have considerable public health importance.
In a prior study, we found that LEAD-X diet could protect male rats from lead accumulation and toxicity. The current study investigates the effects of LEAD-X on maternal, fetal and neonatal lead toxicity in rats during pregnancy and lactation. The objective of this study was to determine the effects of interactions between LEAD-X and lead on erythropoiesis, fetal and neonatal growth, maternal blood pressure, maternal and fetal organ lead concentrations, and lead toxicity during pregnancy and the first week of lactation in rats.
This study is based on the following hypotheses: 1) that basic diet will enhance maternal, fetal and neonatal lead accumulation and toxicity during pregnancy and lactation; 2) that LEAD-X diet will protect the mother, fetus and neonate from lead accumulation and toxicity; 3) that LEAD-X diet will produce a greater reduction in lead toxicity in the fetus and neonate than in the mother; and 4) that LEAD-X will influence the effects of lead on blood pressure during the third trimester of pregnancy.
Each of these hypotheses is supported by the results described below.
MATERIALS AHD METHODS
Animal care. Twelve-week-old female Sprague Dawley rats were allowed to acclimate to the laboratory environment for 1 wk. During this period, daily diet was provided as the supplements taken by women. But in Basic diet group, modified diets contained 0.2% calcium concentrate; in the other two, LEAD-X or EDTA were introduced. The rats continued to have free access to these diets for the remainder of the study.
After the acclimation period, two female rats were caged for 1-3 d with a 13 to 19-wk-old male rat of the same strain. Female rats were examined each morning for the presence of a vaginal plug and removed to a separate cage if one was found. Of 57 female rats caged with the male rats, 49 were successfully impregnated. The day on which the vaginal plug was observed was considered as the first day of pregnancy.
After being identified as pregnant, the 49 rats were randomly assigned to six treatment groups. They continued to have free access to diets containing either Basic diet, LEAD-X and EDTA were given drinking water containing 0 or 250 mg/L of lead. The group fed Basic diet in the diet and exposed to lead contained 9 rats; the other five groups each consisted of 8 rats. Duplicate analysis of the diets showed mean LEAD-X concentrations of 4.9g/100g. Diet lead concentrations were <0.18 μg/g.
Lead acetate was used to prepare the drinking water solution containing 250 mg/L of lead. Sodium acetate trihydrate was added to the water of the groups not given lead at an equivalent acetate concentration. Glacial acetic acid was added to the drinking water solutions at a concentration of 12.5 μL/L to prevent formation and precipitation of lead carbonate. Drinking water consumption was not limited but was monitored. Food and water were made available without restriction to increase the chance for successful full-term pregnancies in each of the six treatment groups.
Laboratory analyses. Blood from the dams, day-old pups and week-old pups was analyzed for lead, hematocrit, free erythrocyte protoporphyrin (FEP) and hemoglobin. The organs harvested were analyzed for lead and the essential divalent metals copper, iron, zinc, calcium and magnesium. All data on lead concentrations and selected concentrations of other metals are reported here.
Whole blood lead concentrations were determined by flameless atomic absorption spectrophotometry. Organ concentrations of Ca, Cu, Fe, Mg and Zn were determined by previously described techniques using flame atomic absorption spectrophotometry.
RESULTS
Body weights for the dams during pregnancy show that weight gain was similar for dams in five of the six treatment groups, but was significantly (p <0.05) lower in the group exposed to lead and fed Basic diet. The 49 dams delivered a total of 629 live and 13 stillborn pups. The number of live pups per litter was between 8-20, and mean numbers of pups per litter were similar, varying between 13.5 and 15.1 for the six treatment groups. Of the pups born live, 297 (47.2%) were female and 332 (52.8%) were male. The gender distribution did not differ significantly among the six treatment groups .Of the 629 pups born live, 606 (96.3%) survived wk 1 of life. Of the 23 that died in the first week, six (26.1%) were in the group exposed to lead and fed the Basic diet and 12 (52.2%) were in the group exposed to lead and fed the EDTA diet; the percent of neonatal deaths differed significantly among the six treatment groups (P < 0.001).
Mean (± SE) daily water consumption was 42 ± 3 ml/d for the group fed Basic diet without lead exposure, 21 + I ml/d for rats fed basic and exposed to lead, 41± 4 ml/d for the group fed LEAD-X diet without lead exposure, 34±1 ml/d for the group fed LEAD-X diet and exposed to lead, 39±2 ml/d for rats fed EDTA without lead exposure and 36±2 ml/d for rats fed EDTA in the diet and exposed to lead. Daily water consumption of the rats fed Basic diets with lead exposure was lower than that of rats in the other live groups. Despite reduced consumption of water containing lead, this group had the highest blood and organ lead concentrations (Fig.1-5). Dams, day-old pups and week-old pups of dams fed EDTA diets had the lowest blood and organ lead concentrations. Whole blood, brain, femur and kidney lead concentrations were higher in the dams than the day or week-old rats, but liver concentrations were similar. Male and female pups had similar blood and organ lead concentrations. Therefore, the results for males and females were combined.
Liver iron concentrations of the dams, day-old pups, and week-old pups (Fig. 6) were reduced by consumption of the EDTA diet. Liver iron in the pups was also influenced by lead; with the highest concentrations occurring in pups fed the LEAD-X diet anti exposed to lead. Significant (P<0.001) reductions in kidney and femur iron concentrations of the dams, day-old pups and week-old pups, as well as reduced brain iron concentrations in pups, Were caused by consumption of the EDTA diet. However, brain iron of the dams was not influenced by dietary Basic diet.
