Iron supplement prevents lead-induced disruption of the blood–brain barrier during rat development

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 μg 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 ultrastructure 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.

The Protein Kinase A Pathway Contributes to Hg2+-Induced Alterations in Phosphorylation and Subcellular Distribution of Occludin Associated with Increased Tight Junction Permeability of Salivary Epithelial Cell Monolayers

“…To investigate whether the increase in paracellular permeability was paralleled by molecular changes in the TJs, we initiated our analysis with the transmembrane protein occludin because 1) it interdigitates with similar occludins from adjacent cells to form the tight junction seal (Feldman et al, 2005); 2) other investigators had already established that occludins respond to heavy metal ions, such as Pb 2ϩ (Wang et al, 2007), which we hypothesized might have similar actions as Hg 2ϩ ; and 3) occludin is a benchmark indicator of TJ permeability (Kevil et al, 2000;Rao et al, 2002;Feldman et al, 2005).…”

Methylmercury Retards the Repair of Wounded Monolayer of Human Brain Microvascular Endothelial Cells by Inhibiting Their Proliferation without Nonspecific Cell Damage

“…10) Lead-a well-known neurotoxic heavy metal-induces cerebral edema and cerebellar hemorrhage via a dysfunction of the blood-brain barrier in the brain of exposed humans and animals, [10][11][12][13] suggesting that the abnormality of blood vessels may cause secondary degeneration of the neurons. Although a similar mechanism is possible in the pathogenesis of MeHg-induced neuropathy in the brain, the toxicity of MeHg to blood vessels has been unclear.…”

Effects of dietary protein levels on the disease resistance, immune function and physical barrier function in the gill of grass carp ( Ctenopharyngodon idella ) after challenged with Flavobacterium columnare

“…However, the effects of dietary protein levels on the TJs of gills or the possible mechanism for such effects in fish have not been addressed in any study. In rats, dietary protein supplements increase the absorption of intestinal iron [29], and Wang et al [30] observed that iron supplementation led to up-regulated mRNA levels of occludin in the brain of rats. In chicks, a low-protein diet elevates the plasma cholesterol level [31], and Zhu et al [32] demonstrated that a high cholesterol level increases MLCK expression in rabbits.…”