Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 258, Issue 3, Pages 394-402Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2011.12.003
Keywords
Mn neurotoxicity; Ebselen; Para-aminosalicylic acid; F-2-lsoprostanes; Prostaglandin E-2; Neuroprotection
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Funding
- National Institutes of Health (NIH) [ES R01 10563]
- I-Med. UL, Faculty of Pharmacy, University of Lisbon
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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-2 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. (C) 2011 Published by Elsevier Inc.
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