Alternative biomarkers of n-hexane exposure: characterization of aminoderived pyrroles and thiol-pyrrole conjugates in urine of rats exposed to 2,5-hexanedione.
Toxicol Lett
; 224(1): 54-63, 2014 Jan 03.
Article
en En
| MEDLINE
| ID: mdl-24459702
ABSTRACT
The identification of pyrrole derivatives in urine of rats exposed to 2,5-hexanedione (2,5-HD), was performed to select an adequate peripheral biomarker predictive of 2,5-HD neurotoxicity. Studies on molecular mechanism of 2,5-HD neurotoxicity have revealed that 2,5-hexanedione reacts with free amino groups of lysine in proteins forming primary pyrrole adducts, which may autoxidize and form pyrrole dimers, responsible for protein crosslinking in neurofilaments, or react with sulfhydryl groups of cysteine in peptides and proteins, forming secondary pyrrole adducts, which probably may inhibit the process responsible by 2,5-HD neurotoxicity. In this work, the analysis of excreted 2,5-HD and pyr-role derivatives in urine of rats i.p. treated with 3 doses of 2,5-HD (400 mg/kg bw/48 h) was performed using ESI-LC-MS/MS. Several pyrrole compounds were identified, namely dimethylpyrrole norleucine(DMPN), cysteine-pyrrole conjugate (DMPN NAC), glutathione-pyrrole conjugate (DMPN GSH) and 2,5-dimethylpyrrole (2,5-DMP). Additionally, free and total 2,5-HD, DMPN and DMPN NAC were quantified. The observed results suggest that DMPN is a sensitive and specific indicator of repeated exposure to 2,5-HD.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirroles
/
Monitoreo del Ambiente
/
Hexanos
/
Hexanonas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Año:
2014
Tipo del documento:
Article