Diazepam influences urinary bioindicator of occupational toluene exposure.
In the present study, we investigated the influence of diazepam (DZP) on the excretion of TOL by examining their urinary metabolites, hippuric acid (HA) and ortho-cresol (o-C). Male Wistar rats were exposed to TOL (20ppm) in a nose-only exposure chamber (6h/day, 5days/week for 6 weeks) with simultaneous administration of DZP (10mg/kg/day). Urinary o-C levels were determined by GC-MS, while HA, creatinine (CR), DZP and its metabolite, nordiazepam, were analysed by HPLC-DAD. The results of a Mann-Whitney U test showed that DZP influenced the urinary excretion of o-C (p<0.05). This pioneering study revealed that there was an interaction between DZP and TOL, probably by the inhibition of the CYP isoforms (CYP2B6, CYP2C8, CYP2E1, and CYP1A2) involved in the oxidative metabolism of the solvent. This is relevant information to be considered in the biomonitoring of occupational toluene exposure.
Laboratory of Toxicant and Drug Analyses, Federal University of Alfenas, Unifal-MG, Alfenas, MG, Brazil.
Alberto Thalison
AT
Silveira
Laboratory of Toxicant and Drug Analyses, Federal University of Alfenas, Unifal-MG, Alfenas, MG, Brazil.
Ana Carolina Campos
ACC
Albuquerque
Laboratory of Occupational Toxicology, Faculty of Pharmaceutical Sciences of Araraquara - FCFAr, UNESP, Araraquara, SP, Brazil.
José Salvador
JS
Lepera
Laboratory of Toxicant and Drug Analyses, Federal University of Alfenas, Unifal-MG, Alfenas, MG, Brazil. Electronic address: isarita.sakakibara@unifal-mg.edu.br.
Isarita
I
Martins
D000395:Air Pollutants, Occupational / Q000378:metabolism / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D003408:Cresols / Q000652:urine*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D019570:Inhalation Exposure / Q000032:analysis*; D007527:Isoenzymes; D008297:Male; D016273:Occupational Exposure / Q000032:analysis*; D017208:Rats, Wistar; D014050:Toluene / Q000378:metabolism / Q000652:urine*
D000395:Air Pollutants, Occupational; D015415:Biomarkers; D003408:Cresols; D007527:Isoenzymes; D014050:Toluene; D003577:Cytochrome P-450 Enzyme System; D003975:Diazepam; C034047:2-cresol
Diazepam; Hippuric acid; Occupational exposure; Toluene; o-Cresol