Teo S, Vore M
Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington 40536.
Toxicol Appl Pharmacol. 1991 Jun 1;109(1):161-70. doi: 10.1016/0041-008x(91)90199-o.
The insecticides mirex and chlordecone suppress the biliary excretion of a wide variety of non-bile acid organic anions in vivo in the rat, and mirex inhibits the uptake of taurocholate (TC), a common bile acid, in isolated rat hepatocytes. We have therefore investigated the effects of mirex and chlordecone on bile acid secretory function (bile flow, bile acid concentration, bile acid secretory rate) in vivo and in the single-pass isolated perfused liver. Male Sprague-Dawley rats were orally dosed with corn oil, mirex (50 mg/kg), or chlordecone (18.75 mg/kg; in vivo studies only) for 3 consecutive days and experiments performed on Day 6. Mirex significantly increased liver weight from 12.2 +/- 0.8 to 20.8 +/- 1.3 g with no change in body weight whereas chlordecone had no significant effect on liver weight (11.9 +/- 0.7 g) or body weight. Mirex significantly decreased while chlordecone increased bile flow per gram liver in vivo; both compounds, however, increased bile flow when expressed per kilogram of body weight. Mirex and chlordecone significantly decreased the bile acid concentration in bile and the bile acid secretory rate (nmol/min/g liver and mumol/min/kg body weight). Studies in the isolated perfused liver were designed to determine the effect of mirex on the ability of the liver to extract increasing concentrations of [3H]TC from the perfusate and excrete it in the bile. Mirex treatment significantly decreased the TC extraction ratio by 40-89% and the hepatic intrinsic clearance by 85-95%. Mirex also significantly decreased the TC-induced choleresis, the concentration of TC in the bile, and the TC secretory rate. The data indicate that mirex treatment markedly inhibits the ability of the liver to extract TC from the blood/perfusate and concentrate it in the bile.
杀虫剂灭蚁灵和开蓬在大鼠体内可抑制多种非胆汁酸有机阴离子的胆汁排泄，并且灭蚁灵可抑制离体大鼠肝细胞对常见胆汁酸牛磺胆酸盐（TC）的摄取。因此，我们研究了灭蚁灵和开蓬对体内及单通道离体灌注肝脏胆汁酸分泌功能（胆汁流量、胆汁酸浓度、胆汁酸分泌速率）的影响。雄性斯普拉格-道利大鼠连续3天经口给予玉米油、灭蚁灵（50毫克/千克）或开蓬（18.75毫克/千克；仅用于体内研究），并在第6天进行实验。灭蚁灵使肝脏重量从12.2±0.8克显著增加至20.8±1.3克，而体重无变化，而开蓬对肝脏重量（11.9±0.7克）或体重无显著影响。在体内，灭蚁灵显著降低而开蓬增加了每克肝脏的胆汁流量；然而，当以每千克体重表示时，两种化合物均增加了胆汁流量。灭蚁灵和开蓬显著降低了胆汁中的胆汁酸浓度和胆汁酸分泌速率（纳摩尔/分钟/克肝脏和微摩尔/分钟/千克体重）。在离体灌注肝脏中的研究旨在确定灭蚁灵对肝脏从灌注液中提取不断增加浓度的[3H]TC并将其排泄到胆汁中的能力的影响。灭蚁灵处理使TC提取率显著降低40 - 89%，肝脏内在清除率显著降低85 - 95%。灭蚁灵还显著降低了TC诱导的胆汁分泌、胆汁中TC的浓度以及TC分泌速率。数据表明，灭蚁灵处理显著抑制了肝脏从血液/灌注液中提取TC并将其浓缩在胆汁中的能力。
