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Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development
Qiang Wang1, Wenjing Luo, Wei Zheng
1Department of Occupational and Environmental Health, Faculty of Military Preventive Medicine, Fourth Military Medical University, 17 Changlexi Street, Xi'an, 710032, China.
Insights
Lead (Pb) exposure damages the blood-brain barrier (BBB) in young animals. Iron (Fe) supplementation protected the BBB integrity and reduced lead accumulation in brain tissues.
Area of Science:
- Neuroscience
- Toxicology
- Pediatrics
Background:
- Children are highly susceptible to lead (Pb) toxicity.
- The immature blood-brain barrier (BBB) is particularly vulnerable to Pb insults, potentially leading to neurodevelopmental issues.
Purpose of the Study:
- To investigate if Pb exposure disrupts the BBB integrity in young animals.
- To determine if iron (Fe) supplementation can prevent Pb-induced BBB disruption.
Main Methods:
- Male Sprague-Dawley rats were exposed to lead acetate in drinking water for 6 weeks.
- Two groups received concurrent iron (FeSO4) supplementation (low and high doses).
- BBB integrity was assessed using electron microscopy and Western blot analysis for occludin expression.
Main Results:
- Pb exposure significantly increased Pb levels in blood and brain tissues.
- Pb exposure disrupted the BBB ultra-structure and reduced occludin expression.
- Fe supplementation maintained BBB integrity, restored occludin levels, and reduced Pb accumulation.
Conclusions:
- Pb exposure damages the BBB in young animals, facilitating Pb accumulation.
- Iron supplementation protects the BBB from Pb-induced damage, offering potential clinical benefits.
Abstract:
Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 microg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO(4) solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p<0.05) and brain tissues by 1.5-2.0-folds (p<0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p<0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications.
