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

A. P. Marreilha dos Santos, Rui L. Lucas, Vanda Andrade, M. Luísa Mateus, Dejan Milatovic, Michael Aschner, M. Camila Batoreu

Research output: Contribution to journalArticle

32 Scopus citations

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 2 prostaglandin (PGE 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.

Original languageEnglish (US)
Pages (from-to)394-402
Number of pages9
JournalToxicology and Applied Pharmacology
Volume258
Issue number3
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

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Keywords

  • Ebselen
  • F -Isoprostanes
  • Mn neurotoxicity
  • Neuroprotection
  • Para-aminosalicylic acid
  • Prostaglandin E

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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