地西泮会影响职业性甲苯暴露的尿液生物标志物。

Diazepam influences urinary bioindicator of occupational toluene exposure.

作者信息

Silveira Alberto Thalison, Albuquerque Ana Carolina Campos, Lepera José Salvador, Martins Isarita

机构信息

Laboratory of Toxicant and Drug Analyses, Federal University of Alfenas, Unifal-MG, Alfenas, MG, Brazil.

Laboratory of Occupational Toxicology, Faculty of Pharmaceutical Sciences of Araraquara - FCFAr, UNESP, Araraquara, SP, Brazil.

出版信息

Environ Toxicol Pharmacol. 2016 Dec;48:191-196. doi: 10.1016/j.etap.2016.10.012. Epub 2016 Oct 18.

DOI:10.1016/j.etap.2016.10.012

PMID:27816004

Abstract

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.

摘要

在本研究中，我们通过检测甲苯（TOL）的尿代谢产物马尿酸（HA）和邻甲酚（o-C），研究了地西泮（DZP）对TOL排泄的影响。将雄性Wistar大鼠置于仅通过鼻腔暴露的实验舱中，暴露于TOL（20ppm）（每天6小时，每周5天，共6周），同时给予DZP（10mg/kg/天）。尿中o-C水平通过气相色谱-质谱联用仪（GC-MS）测定，而HA、肌酐（CR）、DZP及其代谢产物去甲地西泮通过高效液相色谱-二极管阵列检测器（HPLC-DAD）分析。曼-惠特尼U检验结果表明，DZP影响o-C的尿排泄（p<0.05）。这项开创性研究表明，DZP与TOL之间存在相互作用，可能是通过抑制参与该溶剂氧化代谢的细胞色素P450同工酶（CYP2B6、CYP2C8、CYP2E1和CYP1A2）。这是职业性甲苯暴露生物监测中需要考虑的相关信息。