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Title: 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 {mu}g 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{sub 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 themore » 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.« less

Authors:
 [1];  [1];  [2];  [3];  [1];  [1];  [1];  [1];  [1];  [4]
  1. Department of Occupational and Environmental Health, Faculty of Military Preventive Medicine, Fourth Military Medical University, 17 Changlexi Street, Xi'an, 710032 (China)
  2. School of Health Sciences, Purdue University, West Lafayette, IN (United States)
  3. Institute of Microbiology Epidemiology, Academy of Military Medical Siences, Beijing 100071 (China)
  4. Department of Occupational and Environmental Health, Faculty of Military Preventive Medicine, Fourth Military Medical University, 17 Changlexi Street, Xi'an, 710032 (China). E-mail: jy_chen@fmmu.edu.cn
Publication Date:
OSTI Identifier:
20976867
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 219; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2006.11.035; PII: S0041-008X(06)00424-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; BLOOD-BRAIN BARRIER; BRAIN; CHILDREN; DRINKING WATER; HEMOGLOBIN; IRON; IRON SULFATES; LANTHANUM NITRATES; LEAD; PERMEABILITY; RATS; TOXICITY; TRANSFERRIN

Citation Formats

Wang Qiang, Luo Wenjing, Zheng Wei, Liu Yiping, Xu Hui, Zheng Gang, Dai Zhongming, Zhang Wenbin, Chen Yaoming, and Chen Jingyuan. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.11.035.
Wang Qiang, Luo Wenjing, Zheng Wei, Liu Yiping, Xu Hui, Zheng Gang, Dai Zhongming, Zhang Wenbin, Chen Yaoming, & Chen Jingyuan. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development. United States. doi:10.1016/j.taap.2006.11.035.
Wang Qiang, Luo Wenjing, Zheng Wei, Liu Yiping, Xu Hui, Zheng Gang, Dai Zhongming, Zhang Wenbin, Chen Yaoming, and Chen Jingyuan. Thu . "Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development". United States. doi:10.1016/j.taap.2006.11.035.
@article{osti_20976867,
title = {Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development},
author = {Wang Qiang and Luo Wenjing and Zheng Wei and Liu Yiping and Xu Hui and Zheng Gang and Dai Zhongming and Zhang Wenbin and Chen Yaoming and Chen Jingyuan},
abstractNote = {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 {mu}g 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{sub 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.},
doi = {10.1016/j.taap.2006.11.035},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 219,
place = {United States},
year = {Thu Feb 15 00:00:00 EST 2007},
month = {Thu Feb 15 00:00:00 EST 2007}
}
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  • Capsaicin, the irritating agent of red pepper, produces ocular inflammation through a neurogenic mechanism. The present study is concerned with the long-term effects of capsaicin pretreatment on the capacity of the eye to respond to different inflammatory stimuli. Following retrobulbar injection of capsaicin to rabbits the aqueous flare response induced by subsequent infrared irradiation (IR) of the iris, subcutaneously administered alpha-melanocyte-stimulating hormone (alpha-MSH) and exogenously administered prostaglandin E2 (PGE2) was reduced greatly. In the case of IR and alpha-MSH the reduced responsiveness was manifest for several weeks after capsaicin pretreatment, involving first the capsaicin-treated eye, but later also the contralateralmore » control eye. After 2-3 months the aqueous flare response was normal in both eyes. In the case of PGE2 the responsiveness was reduced for a shorter time; after 3 weeks the response was normal in both eyes. The results indicate that all three stimuli tested are at least partly dependent upon an intact sensory innervation to disrupt the blood-aqueous barrier, but that the mechanism of action of PGE2 is different from that of IR and alpha-MSH.« less
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  • To assess the potential of a T1-weighted, gadolinium-enhanced MR technique for quantifying radiation-induced changes of blood-brain barrier permeability in a model of stereotactically implanted intracerebral gliomas in rats. We calculated the gadolinium blood-to-tissue transport coefficient for gadopentetate dimeglumine from signal intensities in sequential MR images in nine control animals that were not irradiated and in five and three animals that had received 2500 cGy and 1500 cGy whole-brain irradiation, respectively, at 2 days before imaging. The average blood-to-tissue transport coefficient values were 9.76 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the control group, 23.41 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in themore » 2500-cGy group, and 25.63 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the 1500-cGy group. Blood-to-tissue transport coefficients were significantly higher after irradiation, indicating increased radiation-induced blood-brain barrier permeability. Similar increased blood-brain barrier leakiness in brain tumors after high-dose irradiation has been shown by previous nuclear medicine studies using quantitative autoradiography. Contrast-enhanced dynamic MR of brain gliomas is a sensitive method to document radiation-induced blood-brain barrier breakdown. Quantitative gadolinium-enhanced MR may become a useful tool for the management of patients with brain tumors undergoing radiation therapy. 28 refs., 4 figs., 1 tab.« less
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