Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: Changes in urinary pyrroles levels and motor activity performance

• N-acetylcysteine intereferes with the excretion of 2,5-HD, DMPN and DMPN NAC.
• N-acetylcysteine decreases urinary free 2,5-HD and DMPN levels.
• N-acetylcysteine increases the cysteine-pyrrole conjugates (DMPN NAC) levels.
• The study shows that N-acetylcysteine protects against neurotoxicity by recovering neurobehavior motor activities.
• DMPN may be proposed as a new specific and sensitive biomarker of 2,5-HD neurotoxicity.

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.