The effect of lead exposure on brain iron homeostasis and the expression of DMT1/FP1 in the brain in developing and aged rats

Zhu, Guo‐Qing; Fan, Guang; Feng, Chenglian; Li, Yanshu; Chen, Ying; Zhou, Fankun; Du, Guihua; Jiao, Huan; Liu, Zhenghua; Xiao, Xinlan; Lin, Fen Fen; Yan, Jing

doi:10.1016/j.toxlet.2012.11.024

Cited by 40 publications

(13 citation statements)

References 49 publications

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“…Therefore, it is unlikely that a specific transporter exists for it. Pb shares the same pathway as Fe because they are both divalent cations, and our previous study has shown that Pb and Fe may share the same transporters, such as the divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) [2]. Iron status may over- or under-regulate intestinal divalent cation transporters and has been suggested specifically with the HFE genotype [3], [4].…”

Section: Introductionmentioning

confidence: 99%

The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

Fan

et al. 2014

PLoS ONE

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BackgroundBoth an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking.ObjectivesTo explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure.MethodsSeven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted.ResultsForty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin.ConclusionsNo C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.

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Section: Introductionmentioning

confidence: 99%

The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

Fan

et al. 2014

PLoS ONE

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“…Because HFE gene is an important modifier of iron, it can also modify lead absorption and storage. As the heavy metal lead shares the same metabolic pathway as iron, the presence of HFE polymorphisms may upregulate or down regulate divalent cation transporters (Zhu et al, 2013;Wright et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Research Article Human Serum Paraoxonase (PON-1) and hemochromatosis gene (HFE) gene polymorphisms in occupationally exposed lead workers from Saudi Arabia

Shaik¹,

Alsaeed²,

Faiyaz-Ul-Haque³

et al. 2019

Genet. Mol. Res.

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Serum paraoxonase (PON1) and hemochromatosis (HFE) genes may play important roles in lead toxicity owing to their role in xenobiotic and iron metabolism, respectively. The association between PON1 and HFE genotypes and blood lead levels (BLLs) was examined in lead exposed subjects from Saudi Arabia. The polymorphisms at PON1 L55M, PON1 Q192R, HFE H63D and HFE C282Y (using PCR-RFLP) and their relation to BLLs was evaluated. The recruited subjects (N = 127) were categorized into low BLL group (<10 μg/dL) and high BLL group (>10 μg/dL) according to CDC guidelines. The low BLL group had a mean level of 3.94 µg/dL, while the high BLL group had levels of 15.33 µg/dL (P < 0.001). Overall, the genetic variants, TA and AA in the PON1 L55M were significantly (P = 0.00002 and P = 0.00322, respectively) associated with a risk of lead toxicity and the allele 'A' was a risk factor (P = 0.00002). However, the Q192R genotype of PON1 along with HFE ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 18 (2): gmr18317 A.P. Shaik et al. 2 H63D and HFE C282Y did not significantly increase the risk of developing lead poisoning. Our findings suggest that L55M gene polymorphism influences the susceptibility of subjects to lead exposure and thus it could be a useful biomarker of genetic susceptibility in assessing an individual's risk of damage from heavy metal exposure.

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“…By its turn DMT1 as well as Ca 2+ channels also transport Mn 2+ [10, 46]. These transporters are present in the kidney, at the BBB endothelium and both glia and neurons [10, 46, 47, 48]. In this study, statistically significant (p<0.05) interaction were noted between Pb and Mn levels in the kidney and brain; In both organs, there was a significant (p<0.05) increase of Pb deposition in the mixture treated group as compared with the Pb single exposed group, while a decrease of Mn in the rats treated with the mixture was attained, when the group was compared with the group only exposed to Mn (Figs.…”

Section: Discussionmentioning

confidence: 99%

Arsenic and Manganese Alter Lead Deposition in the Rat

Andrade

Mateus

Santos

et al. 2014

Biol Trace Elem Res

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Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs. Despite the recognition that metals in a mixture may alter each other’s toxicity by affecting deposition, there is dearth of information on their interactions in vivo. In this work, we investigated the effect of As and Mn on Pb tissue deposition, focusing on the kidney, brain and liver. Wistar rats were treated with 8 doses of each single metal, Pb (5 mg/Kg bw), As (60 mg/L) and Mn mg/Kg bw), or the same doses in a triple metal mixture. Kidney, brain, liver, blood and urine Pb, As and Mn concentrations were determined by graphite furnace atomic absorption spectrophotometry. Pb kidney, brain and liver concentrations in the metal mixture-treated group were significantly increased compared to the Pb alone treated group, being more pronounced in the kidney (5.4 fold), brain (2.5 fold) and liver (1.6 fold). Urinary excretion of Pb in the metal mixture-treated rats significantly increased compared with the Pb treated group, although blood Pb concentrations were analogous to the Pb treated group. Co-treatment with As, Mn and Pb alters Pb deposition compared to Pb alone treatment, increasing Pb accumulation predominantly in kidney and brain. Blood Pb levels, unlike urine, do not reflect the increased Pb deposition in the kidney and brain. Taken together, the results suggest that the nephro- and neurotoxicity of “real-life” Pb exposure scenarios should be considered within the context of metal mixture exposures.

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The effect of lead exposure on brain iron homeostasis and the expression of DMT1/FP1 in the brain in developing and aged rats

Cited by 40 publications

References 49 publications

The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

Research Article Human Serum Paraoxonase (PON-1) and hemochromatosis gene (HFE) gene polymorphisms in occupationally exposed lead workers from Saudi Arabia

Arsenic and Manganese Alter Lead Deposition in the Rat

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