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 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.
authors.affiliation: I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. apsantos@ff.ul.pt
authors.forename: A P Marreilha Dos
authors.initials: AP
authors.lastname: Santos
authors.forename: Rui L
authors.initials: RL
authors.lastname: Lucas
authors.forename: Vanda
authors.initials: V
authors.lastname: Andrade
authors.forename: M Luísa
authors.initials: ML
authors.lastname: Mateus
authors.forename: Dejan
authors.initials: D
authors.lastname: Milatovic
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: M Camila
authors.initials: MC
authors.lastname: Batoreu
mesh_terms: D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D054833:Isoindoles; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D001393:Azoles; D015415:Biomarkers; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; C042986:ebselen; D008345:Manganese; D010131:Aminosalicylic Acid