Title: Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity.
Authors: Santos, A P Marreilha Dos; Lucas, Rui L; Andrade, Vanda; Mateus, M Luisa; Milatovic, Dejan; Aschner, Michael; Batoreu, M Camila
Published In Toxicol Appl Pharmacol, (2012 Feb 1)
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 Eýýý prostaglandin (PGEýýý) 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.
PubMed ID: 22178737
MeSH Terms: Aminosalicylic Acid/pharmacology*; Animals; Azoles/pharmacology*; Behavior, Animal/drug effects; Biological Markers/metabolism; Brain/drug effects; Disease Models, Animal; Inflammation/chemically induced; Inflammation/prevention & control; Male; Manganese/pharmacokinetics; Manganese/toxicity*; Motor Activity/drug effects; Neuroprotective Agents/pharmacology; Neurotoxicity Syndromes/etiology; Neurotoxicity Syndromes/prevention & control*; Organoselenium Compounds/pharmacology*; Oxidative Stress/drug effects; Rats; Rats, Wistar; Tissue Distribution