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Title: Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

Abstract

Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared to rats treated with Mn alone), concomitant with reduced brain E{sub 2} prostaglandin (PGE{sub 2}) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ►more » Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.« less

Authors:
 [1]; ; ;  [1]; ;  [2];  [1]
  1. I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon (Portugal)
  2. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)
Publication Date:
OSTI Identifier:
22215232
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 258; Journal Issue: 3; Other Information: Copyright (c) 2011 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; AMINO ACIDS; BIOLOGICAL MARKERS; BIOLOGICAL STRESS; BLOOD; BODY BURDEN; BRAIN; GLUTATHIONE; IN VIVO; INFLAMMATION; LTH; MANGANESE; OXIDATION; PROSTAGLANDINS; RATS; THERAPY; TOXICITY

Citation Formats

Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt, Lucas, Rui L., Andrade, Vanda, Mateus, M. Luísa, Milatovic, Dejan, Aschner, Michael, and Batoreu, M. Camila. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2011.12.003.
Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt, Lucas, Rui L., Andrade, Vanda, Mateus, M. Luísa, Milatovic, Dejan, Aschner, Michael, & Batoreu, M. Camila. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity. United States. doi:10.1016/J.TAAP.2011.12.003.
Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt, Lucas, Rui L., Andrade, Vanda, Mateus, M. Luísa, Milatovic, Dejan, Aschner, Michael, and Batoreu, M. Camila. Wed . "Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity". United States. doi:10.1016/J.TAAP.2011.12.003.
@article{osti_22215232,
title = {Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity},
author = {Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt and Lucas, Rui L. and Andrade, Vanda and Mateus, M. Luísa and Milatovic, Dejan and Aschner, Michael and Batoreu, M. Camila},
abstractNote = {Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared to rats treated with Mn alone), concomitant with reduced brain E{sub 2} prostaglandin (PGE{sub 2}) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ► Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.},
doi = {10.1016/J.TAAP.2011.12.003},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 258,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2012},
month = {Wed Feb 01 00:00:00 EST 2012}
}