title: Comparison between 5-aminosalicylic acid (5-ASA) and para-aminosalicylic acid (4-PAS) as potential protectors against Mn-induced neurotoxicity.
abstract: Manganese (Mn) is an essential metal for biological systems; however, occupational or clinical exposure to high levels of Mn can produce a neurological disorder called manganism. Oxidative stress and neuroinflammation play major roles in the Mn-induced neurodegeneration leading to dysfunction of the basal ganglia. We investigated the toxic effects of MnCl2 in an immortalized rat brain endothelial cell line (RBE4) and the protective effects of the radical scavenging aminosalicylic acids, 5-aminosalicylic acid (5-ASA) and 4-aminosalicylic acid (4-PAS). Mn cytotoxicity was determined with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) activity. A significant decrease in MTT reduction concomitant with increased LDH release was noted in RBE4 cells exposed for 24 h to MnCl2 (600 and 800 μM; p < 0.0001). Our results establish that compared to 4-PAS, 5-ASA has greater efficacy in protecting RBE4 cells from Mn-induced neurotoxicity after preexposure to MnCl2 800 μM (p < 0.0001).
authors: I-Med. UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
authors: Dinamene
authors: D
authors: Santos
authors: M Camila
authors: MC
authors: Batoreu
authors: Michael
authors: M
authors: Aschner
authors: Ana P
authors: AP
authors: Marreilha dos Santos
mesh_terms: D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008345:Manganese / Q000633:toxicity*; D017895:Manganese Compounds; D020149:Manganese Poisoning / Q000209:etiology / Q000517:prevention & control*; D019804:Mesalamine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D018696:Neuroprotective Agents; D008345:Manganese; D019804:Mesalamine; D010131:Aminosalicylic Acid; D007770:L-Lactate Dehydrogenase; C025340:manganese chloride