title: Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: changes in urinary pyrroles levels and motor activity performance.
abstract: The interference of N-acetylcysteine (NAC) on 2,5-hexanedione (2,5-HD) neurotoxicity was evaluated through behavioral assays and the analysis of urinary 2,5-HD, dimethylpyrrole norleucine (DMPN), and cysteine-pyrrole conjugate (DMPN NAC), by ESI-LC-MS/MS, in rats exposed to 2,5-HD and co-exposed to 2,5-HD and NAC. Wistar rats were treated with 4 doses of: 400mg 2,5-HD/kg bw (group I), 400mg 2,5-HD/kg bw+200mg NAC/kg bw (group II), 200mg NAC/kg bw (group III) and with saline (group IV). The results show a significant decrease (p<0.01) in urinary DMPN and free 2,5-HD, a significant increase (p<0.01) in DMPN NAC excretion, and a significant recovery (p<0.01) on motor activity in rats co-exposed to 2,5-HD+NAC, as compared with rats exposed to 2,5-HD alone. Taken together, our findings suggest that at the studied conditions NAC protects against 2,5-HD neurotoxicity and DMPN may be proposed as a new sensitive and specific biomarker of 2,5-HD neurotoxicity in animals treated with a toxic amount of 2,5-hexanedione.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; CiiEM, Center for Interdisciplinary Research Egas Moniz, ISCSEM, Institute of Health and Life Sciences Egas Moniz, Campus Universitário, Quinta da Granja, 2829-511 Caparica, Portugal.
authors.forename: M Edite
authors.initials: ME
authors.lastname: Torres
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: A P Marreilha
authors.initials: AP
authors.lastname: dos Santos
authors.affiliation: CiiEM, Center for Interdisciplinary Research Egas Moniz, ISCSEM, Institute of Health and Life Sciences Egas Moniz, Campus Universitário, Quinta da Granja, 2829-511 Caparica, Portugal.
authors.forename: Luísa L
authors.initials: LL
authors.lastname: Gonçalves
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Vanda
authors.initials: V
authors.lastname: Andrade
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: M Camila
authors.initials: MC
authors.lastname: Batoréu
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. Electronic address: lmateus@ff.ul.pt.
authors.forename: M Luísa
authors.initials: ML
authors.lastname: Mateus
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002853:Chromatography, Liquid; D006588:Hexanones / Q000008:administration & dosage* / Q000633:toxicity / Q000652:urine; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D009498:Neurotoxins / Q000008:administration & dosage* / Q000633:toxicity / Q000652:urine; D009646:Norleucine / Q000652:urine; D011758:Pyrroles / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D006588:Hexanones; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011758:Pyrroles; D009646:Norleucine; C011269:2,5-hexanedione; D000111:Acetylcysteine
keywords: 2,5-Hexanedione; Behavioral assays; LC–MS/MS; N-acetylcysteine; Pyrrole compounds; Urinary biomarkers