Zalups R K, Barfuss D W
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207 USA.
Drug Metab Dispos. 1996 Apr;24(4):480-6.
In the present study, we tested the hypothesis that diversion of biliary flow from the liver to the intestines (using biliary cannulation) or prevention of biliary outflow from the liver ( by biliary ligation) affects significantly the renal uptake and accumulation of mercury in rats given an intravenous nontoxic (0.5 mumol/kg) dose of mercuric chloride (containing 203 HgCl2). Diverting biliary flow away from the small intestine, by cannulation of the bile duct, caused a significant increase in the content of mercury in the blood and caused a significant decrease in the total renal uptake of mercury at 1 and 3 hr after the injection of mercuric chloride. By the end of 3 hr after the injection of mercury, the amount of mercury that was not taken up by the kidneys, as a result of diversion of biliary flow, was approximately 10% of the administered dose. The decreased renal uptake of mercury was caused by decreased uptake of mercury in the renal cortex and outer stripe of the outer medulla. Interestingly, very little mercury was excreted in the bile. Only approximately 0.19% of the administered dose of mercury was excreted in the bile in 3 hr. Renal accumulation of mercury, particularly in the cortex and outer stripe of the outer medulla, was also reduced significantly after biliary ligation, when evaluated 24 hr after the injection of inorganic mercury. There was an almost 3-fold increase in the content of mercury in the liver of the rats whose bile duct had been ligated. Fecal excretion of mercury was also diminished in these animals. It was interesting, however, that these rats did excrete some mercury in the feces. Dispositional data obtained from the segments of the gastrointestinal tract indicate that fecal excretion of mercury in the rats whose bile duct had been ligated was most likely caused by intestinal secretion of mercury. In conclusion, the present findings indicate that a hepato-biliary-enteric metabolic pathway plays a role in some aspect of the renal accumulation of administered inorganic mercury. This role does not, however, seem to involve, to any significant degree, the biliary and enteric processing of mercury secreted into the bile.
在本研究中，我们检验了以下假设：将胆汁从肝脏引流至肠道（通过胆管插管）或阻止胆汁从肝脏流出（通过胆管结扎）会显著影响静脉注射无毒剂量（0.5 μmol/kg）氯化汞（含203HgCl2）的大鼠体内汞的肾脏摄取和蓄积。通过胆管插管使胆汁从小肠分流，导致血液中汞含量显著增加，并使注射氯化汞后1小时和3小时时肾脏对汞的总摄取量显著降低。注射汞后3小时结束时，由于胆汁分流，未被肾脏摄取的汞量约为给药剂量的10%。肾脏对汞摄取的减少是由于肾皮质和外髓质外层条带中汞摄取的减少所致。有趣的是，胆汁中汞的排泄量极少。在3小时内，仅约0.19%的给药剂量汞从胆汁中排泄。在注射无机汞24小时后评估，胆管结扎后肾脏中汞的蓄积，尤其是在肾皮质和外髓质外层条带中的汞蓄积也显著减少。胆管结扎的大鼠肝脏中汞含量几乎增加了3倍。这些动物粪便中汞的排泄也减少。然而，有趣的是，这些大鼠确实会在粪便中排泄一些汞。从胃肠道各段获得的处置数据表明，胆管结扎大鼠粪便中汞的排泄很可能是由肠道汞分泌引起的。总之，目前的研究结果表明，肝-胆-肠代谢途径在给药无机汞的肾脏蓄积的某些方面发挥作用。然而，这一作用似乎在很大程度上并不涉及分泌到胆汁中的汞的胆汁和肠道处理过程。
