Payan J P, Beydon D, Fabry J P, Morel G, Brondeau M T, Ban M, De Ceaurriz J
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
J Appl Toxicol. 1993 Jan-Feb;13(1):19-24. doi: 10.1002/jat.2550130106.
Male Sprague Dawley rats with cannulated bile duct (BDC rats) received 100 or 200 mg kg-1 labelled hexachloro-1,3-butadiene ([14C]HCBD) by gavage 1 h (BDC1 rats) or 24 h (BDC24 rats) after surgical cannula implantation. Twenty-four hours after treatment with HCBD, rats were examined histochemically and biochemically for kidney damage. Urine, faeces, liver and kidney radioactivities were also measured in 24-h samples. Results were compared with those obtained from non-cannulated (NC) rats. Bile-duct cannulation did not completely protect against HCBD-induced kidney damage. The 24-h [14C] urinary excretion and tissue content was 30-50% lower in BDC rats compared to NC rats and correlated well with the toxicity findings. BDC1 rats appeared to be much more resistant to HCBD treatment than BDC24 rats. Since faecal [14C] radioactivity extractable by diethyl ether at neutral pH in BDC1 rats was twice that measured in BDC24 rats, the greater resistance was attributed to a higher deficiency in the gastrointestinal absorption of unchanged HCBD. The present results reveal that the biliary metabolites of HCBD are not solely responsible for kidney toxicity as previously assumed. They suggest a sinusoidal efflux of the HCBD conjugates from the liver.
对具有插管胆管的雄性斯普拉格-道利大鼠（BDC大鼠）在手术植入插管后1小时（BDC1大鼠）或24小时（BDC24大鼠）经口灌胃给予100或200mg/kg标记的六氯-1,3-丁二烯（[14C]HCBD）。用HCBD处理24小时后，对大鼠进行肾脏损伤的组织化学和生物化学检查。还测定了24小时样本中的尿液、粪便、肝脏和肾脏放射性。将结果与未插管（NC）大鼠获得的结果进行比较。胆管插管不能完全预防HCBD诱导的肾脏损伤。与NC大鼠相比，BDC大鼠24小时的[14C]尿排泄量和组织含量低30-50%，且与毒性结果密切相关。BDC1大鼠似乎比BDC24大鼠对HCBD处理更具抗性。由于BDC1大鼠在中性pH下可被乙醚提取的粪便[14C]放射性是BDC24大鼠的两倍，因此更大的抗性归因于未改变的HCBD在胃肠道吸收方面的更高缺陷。目前的结果表明，HCBD的胆汁代谢产物并非如先前假设的那样是肾脏毒性的唯一原因。它们提示HCBD共轭物从肝脏的窦状隙流出。
