Effect of Maternal Lead Exposure on Craniofacial Ossification in Rat Fetuses and the Role of Antioxidant Therapy (original) (raw)
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Skeletal Effects of Developmental Lead Exposure in Rats
Toxicological Sciences, 2001
To identify possible direct and indirect mechanisms underlying the effects of lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and 1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475 ppm lead acetate in the drinking water from gestational day 4 to euthanasia on day 55. Tibial strength was tested by 3-point bending and plasma levels of vitamin D metabolites were measured. A dose-dependent decrease of the load to failure was demonstrated but only in male pups. No differences in plasma levels of vitamin D metabolites were observed. In the second study, conducted to test if hormone treatment would attenuate the lead deficits, male and female pups were exposed to 0 or 2475 ppm lead acetate and then, from 30-60 days of age, received either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone (DHT, males only), or estradiol (females only). Lead exposure significantly reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period. Sex steroid replacement did not restore skeletal parameters in lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF(1)) concentrations, rates of bone growth, and bone strength measures in controls while having no effect in lead-exposed pups. The third study was conducted at 100 days of age, when endocrine parameters have been shown to be normalized, to test for effects of lead exposure on bone formation during tibial limb lengthening (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new endosteal bone formation were decreased in the distraction gaps of the lead-treated animals (p < 0.01). In conclusion, lead exposure reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period, and these effects could not be reversed by a growth hormone (GH) axis stimulator or by sex-appropriate hormones. Finally, lead exposure appears to specifically inhibit osteoblastogenesis in vivo in adult animals.
Calcified Tissue International, 1997
The effect of exposure to lead on the longitudinal development of bone and on bone mass was studied in rats. A group of 35, 50-day-old female Wistar rats was divided into a control group of 15 rats and an experimental group of 20 rats fed a diet supplemented with 17 mg of lead acetate per kg feed for 50 days. Total body bone densitometry (TBBMC) was performed the day before ending the 50-day experiment. On day 50, all rats were killed and their right femur and 5th lumbar vertebra were dissected. The bones were cleaned of soft tissue and femoral length and vertebral length were measured with a caliper and all bones were weighed on a precision scale. Final body weight (P < 0.05), TBBMC (P < 0.005), and femur weight (P < 0.005) were significantly lower in the control group. Femur length did not differ between groups, but the length of the 5th lumbar vertebra was greater in the control group (P < 0.05). Histomorphometry of the femur showed that Cn-BV/TV, Tb-N, Tb-Th were lower (P < 0.05 in all) and Tb-Sp was higher (P < 0.05) in the group given the lead-supplemented diet. These findings suggested lead-induced inhibition of axial bone development and a histomorphometric decrease in bone mass, produced mainly by enhanced resorption, and a densitometric increase in bone mass, produced by lead accumulation in bone.
Reduced Bone and Body Mass in Young Male Rats Exposed to Lead
BioMed Research International, 2014
The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28-or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D) and 60 days (60D) in control (C) and in lead-exposed animals (Pb). Lead measurements were made by GF-AAS. There was no significant difference ( > 0.05) in the concentration of whole blood lead between Pb-28D (8.0 ± 1.1 g/dL) and Pb-60D (7.2 ± 0.89 g/dL), while both significantly varied ( < 0.01) from controls (0.2 g/dL). Bone lead concentrations significantly varied between the Pb-28D (8.02 ± 1.12 g/g) and the Pb-60D (43.3 ± 13.26 g/g) lead-exposed groups ( < 0.01), while those exposed groups were also significantly higher ( < 0.0001) than the 28D and 60D control groups (Pb < 1 g/g). The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D), which reinforces the importance of using bone lead as an exposure biomarker.
The Effects of Ascorbic Acid and Garlic on Bone Mineralization in Lead Exposed Pregnant Rats
Background: Lead exposure during pregnancy may impair skeletal development. Oxidative stress is one of the important mechanisms for lead toxicity effects. The aim of this study was to investigate ascorbic acid and garlic effects on bone mineralization in lead exposed pregnant rats. Materials and Methods: In this experimental study, 50 pregnant Wistar rats were randomly divided into 5 groups; group (L) exposed to lead acetate, group (L+C) exposed to lead acetate and ascorbic acid (vitamin C), group (L+G) exposed to lead acetate and garlic juice, sham group treated with tap water plus 0.4 mL/L normal hydrogen chloride (HCl) and 0.5 mg/L sugar, control group without any intervention. All treatments were done during pregnancy. After birth, blood and bone lead levels were measured and then all neonates were sacrificed, and their right tibia bone processed for alizarin red and Alcian blue staining. Results: Blood lead levels in L group increased significantly in both mothers and their neonate compared to control animals. In addition, the neonates born to L group showed markedly higher lead concentrations in their bone than that of controls. In contrast, we found no significant changes in blood and bone lead levels in lead exposed neonates that received ascorbic acid and garlic. Bone formation in neonates of L group was clearly disrupted. Interestingly, both ascorbic acid and garlic treatments could apparently improve bone formation during pregnancy in lead exposed neonates. Conclusion: Ascorbic acid and garlic consumption during pregnancy may improve the deleterious effects of lead exposure on bone mineralization.
Effect of Vitamin C on Xenobiotic Metabolism and Histopathology of Fetal Brain of Lead Exposed Mice
2014
The objectives of this study are to investigate the effect of vitamin C on xenobiotic metabolism and histopathology of fetalbrain of mice after exposed to lead. The experiment used 27 pregnant mice and divided into three groups: the negative control group (NC), which wastreated with distilled water, the positive control group (PC) was exposed to 25 mg Pb/kg body weight (BW)/day, and the third group (T) was exposed to 25 mg Pb/kg BW/day during gestation day 7 to 16 and then administered with 64 mg vitamin C/kg BW/day started on the gestation day 9 to 16. Both lead and vitamin C were given to mice orally. The result showed that supplementationof vitaminCprovided protectionto thefetus. The histological structure of fetal brain administered to vitamin C (T) was betterthan PC. Theaverage concentration of lead inits fetal head (T) is the lowestamongthe othergroups.Supplementation of vitamin C can protect liver and fetuses, suggesting that vitamin C could bind the lead and excrete it via u...
The effect of lead on bone mineral properties from female adult C57/BL6 mice
Bone, 2010
Lead toxicity is a significant problem in the U.S. with elevated blood lead levels being highest among very young children and older adults > 50 years old. Bone is the major reservoir of body lead, accounting for 75% in children and 90% in adults. Very little is known about the effect of lead on bone mineral properties in adults. We investigated the effect of lead on the femora from adult, 6 month old female C57/BL6 mice who were administered lead in the drinking water (250 ppm, blood lead 33 μg/dl) for 4 months. Bone mineral properties were examined using Fourier Transform Infrared Microscopy (FTIRM), quantitative microcomputed tomography (microCT) and whole bone mechanical testing. Lead significantly decreased the bone mineral density in the cortical and proximal cancellous bone and increased the marrow area in the cortical bone with microCT. Whole bone three-point bending showed a trend of decreased maximum and failure moments in the lead treated bones compared to controls. Lead significantly decreased the mineral/ matrix ratio, collagen maturity and crystallinity in the trabecular bone as measured by FTIRM. In the cortical bone lead significantly decreased collagen maturity and bone crystal size by FTIRM. In contrast to cell culture studies, lead significantly increased serum osteocalcin levels. Lead also significantly increased the bone formation and resorption markers suggesting increased bone turnover. These data show lead increases bone turnover resulting in weaker cortical bone in adult female mice and suggest that lead may exacerbate bone loss and osteoporosis in the elderly.
Decrease in Birth Weight in Relation to Maternal Bone-Lead Burden
PEDIATRICS, 1997
Objective. A number of prospective studies have examined lead levels in umbilical cord blood at birth as predictors of infant mental development. Although several have found significant inverse associations, others have not. Measurement of lead levels in maternal bone, now recognized as the source of much fetal exposure, has the potential to serve as a better or complementary predictor of lead's effect on the fetus. Our objective was to compare lead levels in umbilical cord blood and maternal bone as independent predictors of infant mental development using a prospective design.
The Journal of nutrition, 1995
We studied the effects of dietary calcium and lead exposure on lead toxicity, fetal and neonatal growth, erythropoiesis and blood pressure during pregnancy and lactation in rats. Pregnant Sprague-Dawley rats (n = 43) were randomly assigned to one of six treatment groups of 7-8 rats each. Half of the rats were fed diets of low (0.1%), normal (0.5%) or high (2.5%) calcium as calcium carbonate and exposed to 250 mg/L of lead in their drinking water for the duration of the pregnancy and for 1 wk of lactation. Three control groups were fed the same diets without lead exposure. Pups were studied at 1 d and 1 wk of age. Maternal and fetal blood and organ samples from the groups fed the low calcium diet had the highest lead concentrations, whereas the lowest lead concentrations were found in the groups fed the high calcium diet. Dam and pup hemoglobin concentrations, hematocrits, and body weights and lengths were reduced by lead exposure and by the high calcium diet. The latter also reduced...
Impact of Bone Lead and Bone Resorption on Plasma and Whole Blood Lead Levels during Pregnancy
American Journal of Epidemiology, 2004
The authors tested the hypotheses that maternal bone lead burden is associated with increasing maternal whole blood and plasma lead levels over the course of pregnancy and that this association is modified by rates of maternal bone resorption. A total of 193 Mexican women were evaluated (1997)(1998)(1999) in the first, second, and third trimesters of pregnancy. Whole blood lead and plasma lead levels were measured in each trimester. Urine was analyzed for cross-linked N-telopeptides (NTx) of type I collagen, a biomarker of bone resorption. Patella and tibia lead levels were measured at 4 weeks postpartum. The relation between whole blood, plasma, and bone lead and NTx was assessed using mixed models. Plasma lead concentrations followed a U-shape, while NTx levels increased significantly during pregnancy. In a multivariate model, the authors observed a significant and positive interaction between NTx and bone lead when plasma lead was used as the outcome variable. Dietary calcium intake was inversely associated with plasma lead. Results for whole blood lead were similar but less pronounced. These results confirm previous evidence that bone resorption increases during pregnancy, with a consequential significant release of lead from bone, constituting an endogenous source of prenatal exposure. They also provide a rationale for testing strategies (e.g., nutritional supplementation with calcium) aimed at decreasing prenatal lead exposure. . (*Participants/nonparticipants with/without urinary measurements of cross-linked N-telopeptides (NTx) of type I collagen.) by guest on November 27, 2015 http://aje.oxfordjournals.org/ Downloaded from Changes in Plasma and Blood Lead Levels during Pregnancy 671 Am J Epidemiol 2004;160:668-678
Release of lead from bone in pregnancy and lactation
Environmental Research, 2003
Concentrations and isotope ratios of lead in blood, urine, 24-h duplicate diets, and hand wipes were measured for 12 women from the second trimester of pregnancy until at least 8 months after delivery. Six bottle fed and six breast fed their infants. One bottle feeder fell pregnant for a second time, as did a breast feeder, and each was followed semicontinuously for totals of 44 and 54 months, respectively. Bone resorption rather than dietary absorption controls changes in blood lead, but in pregnancy the resorption of trabecular and cortical bone are decoupled. In early pregnancy, only trabecular bone (presumably of low lead content) is resorbed, causing blood leads to fall more than expected from hemodilution alone. In late pregnancy, the sites of resorption move to cortical bone of higher lead content and blood leads rise. In bottle feeders, the cortical bone contribution ceases immediately after delivery, but any tendency for blood leads to fall may be compensated by the effect of hemoconcentration produced by the postpartum loss of plasma volume. In lactation, the whole skeleton undergoes resorption and the blood leads of nursing mothers continue to rise, reaching a maximum 6-8 months after delivery. Blood leads fall from pregnancy to pregnancy, implying that the greatest risk of lead toxicity lies with first pregnancies.