TY - JOUR
T1 - Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model
T2 - Changes in urinary pyrroles levels and motor activity performance
AU - Torres, M. Edite
AU - dos Santos, A. P.Marreilha
AU - Gonçalves, Luísa L.
AU - Andrade, Vanda
AU - Batoréu, M. Camila
AU - Mateus, M. Luísa
N1 - Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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: 400 mg 2,5-HD/kg bw (group I), 400 mg 2,5-HD/kg bw + 200 mg NAC/kg bw (group II), 200 mg 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.
AB - 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: 400 mg 2,5-HD/kg bw (group I), 400 mg 2,5-HD/kg bw + 200 mg NAC/kg bw (group II), 200 mg 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.
KW - 2,5-Hexanedione
KW - Behavioral assays
KW - LC-MS/MS
KW - N-acetylcysteine
KW - Pyrrole compounds
KW - Urinary biomarkers
UR - http://www.scopus.com/inward/record.url?scp=84907971187&partnerID=8YFLogxK
U2 - 10.1016/j.etap.2014.09.008
DO - 10.1016/j.etap.2014.09.008
M3 - Article
C2 - 25305742
AN - SCOPUS:84907971187
SN - 1382-6689
VL - 38
SP - 807
EP - 813
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
IS - 3
ER -