六氯-1,3-丁二烯的处置与肾毒性

Disposition and nephrotoxicity of hexachloro-1,3-butadiene.

作者信息

Davis M E, Berndt W O, Mehendale H M

出版信息

Toxicology. 1980;16(3):179-91. doi: 10.1016/0300-483x(80)90115-8.

Abstract

Hexachloro-1,3-butadiene (HCBD) administration to rats results in impaired kidney function. The time course of nephrotoxicity and disposition of HCBD were examined. Within 4 h after HCBD (300 mg/kg, i.p.) compromised kidney function was found as decreased urine osmolality, glomerular filtration rate (GFR) and drug excretion. At 24 h elevated blood urea nitrogen (BUN) was found. However, no definitive signs of hepatotoxicity were observed up to 48 h after HCBD. Control ralts excreted 40% of tracer dose (0.1 mg/kg, i.p.) of [14C]HCBD in feces and 30% in urine in 48 h. Rats with HCBD-induced nephrotoxicity excreted much less, 7% in feces and 6% in urine. Aliquots of these samples were extracted with hexane. All of 14C in bile and 87% of that in urine was water soluble, indicating that HCBD was biotransformed into polar metabolites.

摘要

给大鼠施用六氯-1,3-丁二烯（HCBD）会导致肾功能受损。研究了HCBD的肾毒性时间进程及其处置情况。在腹腔注射HCBD（300mg/kg）后4小时内，发现肾功能受损，表现为尿渗透压、肾小球滤过率（GFR）和药物排泄降低。在24小时时，发现血尿素氮（BUN）升高。然而，在HCBD注射后48小时内未观察到明确的肝毒性迹象。对照大鼠在48小时内将示踪剂量（0.1mg/kg，腹腔注射）的[14C]HCBD的40%经粪便排泄，30%经尿液排泄。HCBD诱导的肾毒性大鼠排泄量少得多，粪便中为7%，尿液中为6%。这些样品的等分试样用己烷萃取。胆汁中所有的14C以及尿液中87%的14C是水溶性的，这表明HCBD被生物转化为极性代谢物。