Maternal–fetal Distribution of Manganese in the Rat Following Inhalation Exposure to Manganese Sulfate

Dorman, David C.; McElveen, Anna M; Marshall, Marianne W.; Parkinson, Carl U.; James, R. Arden; Struve, Melanie F.; Wong, Brian A.

doi:10.1016/j.neuro.2004.08.004

Cited by 31 publications

(8 citation statements)

References 22 publications

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“…Metal concentrations in the blood and brain of pups were all elevated compared to their controls. Although the placental or milk levels of Mn or Pb were not measured, the transfer of Mn across the placenta and the excretion of Mn into milk was previously demonstrated (Dorman et al, 2005a). Dorman et al .…”

Section: Discussionmentioning

confidence: 99%

Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring

Molina¹,

Phattanarudee

Kim

et al. 2011

NeuroToxicology

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Manganese (Mn) and lead (Pb) exposures during developmental period can impair development by direct neurotoxicity or through interaction with iron metabolism. Therefore, we examined the effects of maternal ingestion of Mn or Pb in drinking water during gestation and lactation on iron metabolism as well as behavior in their offspring. Pregnant dams were given distilled water, 4.79 mg/ml Mn, or 2.84 mg/ml Pb in drinking water during gestation and lactation. Pups were studied at time of weaning for 59Fe absorption from the gut, duodenal Divalent Metal Transporter 1 (DMT1) expression, hematological parameters, and anxiety-related behavior using an Elevated Plus Maze (EPM) test. Metal-exposed pups had lower body weights and elevated blood and brain concentrations of the respective metal. Pb-exposed pups had lower hematocrits and higher blood Zn protoporphyrin levels. In contrast, Mn exposed pups had normal hematological parameters but significantly reduced Zn protoporphyrin. Pharmacokinetic studies using 59Fe showed that intestinal absorption in metal-exposed pups was not different from controls, nor was it correlated with duodenal DMT1 expression. However, intravenously injected 59Fe was cleared more slowly in Pb-exposed pups resulting in higher plasma levels. The overall tissue uptake of 59Fe was lower in Mn-exposed and lower in the brain in Pb-exposed pups. The EPM test demonstrated that Mn-exposed, but not Pb-exposed, pups had lower anxiety-related behavior compared to controls. We conclude that gestational and lactational exposures to Mn or Pb differentially alter Fe metabolism and anxiety-related behavior. The data suggest that perturbation in Fe metabolism may contribute to the pathophysiologic consequences of Mn and Pb exposure during early development.

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Section: Discussionmentioning

confidence: 99%

Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring

Molina¹,

Phattanarudee

Kim

et al. 2011

NeuroToxicology

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“…The International Commission on Radiological Protection (ICRP) has reported approximately 40% of body Mn accumulates in bone (ICRP, 1972). Information from animal studies of Mn accumulation in bone can be found in literature, albeit is very limited (Dorman et al, 2005; Seaborn and Nielsen, 2002). Using a physiologically-based pharmacokinetic modeling approach, Andersen et al (1999) reported that Mn stored in bone tissues contributed to over 40% of body Mn; the estimate is closer to the aforementioned human data.…”

Section: Introductionmentioning

confidence: 99%

Manganese accumulation in bone following chronic exposure in rats: Steady-state concentration and half-life in bone

O’Neal

Hong

et al. 2014

Toxicology Letters

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Literature data indicate that bone is a major storage organ for manganese (Mn), accounting for 43% of total body Mn. However, the kinetic nature of Mn in bone, especially the half-life (t1/2), remained unknown. This study was designed to understand the time-dependence of Mn distribution in rat bone after chronic oral exposure. Adult male rats received 50 mg Mn/kg (as MnCl2) by oral gavage, 5 days per week, for up to 10 weeks. Animals were sacrificed every two weeks during Mn administration for the uptake study, and on day 1, week 2, 4, 8, or 12 after the cessation at 6-week Mn exposure for the t1/2 study. Mn concentrations in bone (MnBn) were determined by AAS analysis. By the end of 6-week’s treatment, MnBn appeared to reach the steady state (Tss) level, about 2–3.2 fold higher than MnBn at day 0. Kinetic calculation revealed t1/2s of Mn in femur, tibia, and humerus bone of 77 (r=0.978), 263 (r=0.988), and 429 (r=0.994) days, respectively; the average t1/2 in rat skeleton was about 143 days, equivalent to 8.5 years in human bone. Moreover, MnBn were correlated with Mn levels in striatum, hippocampus, and CSF. These data support MnBn to be a useful biomarker of Mn exposure.

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“…13,16,19 The rat placenta effectively limited Mn delivery to the fetus including the brain. 19,20 At similar exposure concentrations, neonatal rats developed brain Mn concentrations comparable to levels seen in young male rats, non-pregnant female rats, and senescent rats. 13,19,21 Particle solubility influenced Mn pharmacokinetics, with inhalation of the more soluble sulfate form resulting in higher brain Mn concentrations than the less soluble phosphate or oxide forms.…”

mentioning

confidence: 86%

Modeling Manganese Kinetics for Human Health Risk Assessment

Yoon¹,

Taylor²,

Clewell³

et al. 2014

Manganese in Health and Disease

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Manganese (Mn) is an essential element, present in significant concentrations in the central nervous system (CNS) and all other tissues. 1-4 Mn is required for normal immune function, regulation of blood sugar and cellular energy, lipid and carbohydrate metabolism, skeletal cartilage development, reproduction, and brain functions. It participates in metabolic pathways and a co-factor metal for Mn superoxide dismutase and glutamine synthetase. 5,6 The body's requirements for Mn are met through food and drinking water, with adult human consumption ranging from 1 to 10 mg Mn per day, of which about 1-5% is absorbed in the gut. 2,5,7 Homeostatic mechanisms controlling uptake, storage, and elimination of dietary Mn maintain tissue Mn concentrations at a relatively constant level despite widely varying dietary levels of Mn.

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Maternal–fetal Distribution of Manganese in the Rat Following Inhalation Exposure to Manganese Sulfate

Cited by 31 publications

References 22 publications

Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring

Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring

Manganese accumulation in bone following chronic exposure in rats: Steady-state concentration and half-life in bone

Modeling Manganese Kinetics for Human Health Risk Assessment

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