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Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2012 Feb 01; Vol. 258 (3), pp. 394-402. Date of Electronic Publication: 2011 Dec 09. - Publication Year :
- 2012
-
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 E₂ prostaglandin (PGE₂) 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.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Behavior, Animal drug effects
Biomarkers metabolism
Brain drug effects
Disease Models, Animal
Inflammation chemically induced
Inflammation prevention & control
Isoindoles
Male
Manganese pharmacokinetics
Motor Activity drug effects
Neuroprotective Agents pharmacology
Neurotoxicity Syndromes etiology
Oxidative Stress drug effects
Rats
Rats, Wistar
Tissue Distribution
Aminosalicylic Acid pharmacology
Azoles pharmacology
Manganese toxicity
Neurotoxicity Syndromes prevention & control
Organoselenium Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 258
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 22178737
- Full Text :
- https://doi.org/10.1016/j.taap.2011.12.003