High‐density lipoproteins decrease the biliary concentration of chlordecone in isolated perfused pig liver

Abstract

Chlordecone (CD) is an organochlorine pesticide associated with albumin and high‐density lipoproteins (HDL) in the plasma. It is found in higher concentrations in the liver than in other tissues and is excreted in the bile. The influence of plasma HDL on the biliary excretion of CD was studied using isolated pig liver perfused with a Krebs‐Ringer bicarbonate solution containing albumin, dextrose, and pig red blood cells. Within 5 min after administration into the perfusion medium of [ ¹⁴ C]CD bound to albumin or to HDL, only 13% of the [ ¹⁴ C]CD dose remained in the perfusate, showing that CD is rapidly taken up by the liver. After 60 min the plasma concentration was constant at 0.008% dose/ml when [ ¹⁴ C]CD was administered bound to albumin in the absence of HDL and at 0.004% dose/ml when administered bound to HDL. The mean concentration of CD in the bile was higher when CD was administered bound to albumin in the absence of HDL (0.039% dose/ml) than when it was administered bound to HDL (0.010% dose/ml). The elimination rate constant of CD from the liver into the bile was 0.007/min whether CD was administered bound to albumin or to HDL. The addition of HDL to the perfusion system after the administration of albumin‐bound CD resulted in lower biliary CD concentrations. The results suggest that HDL affects the distribution of CD between the perfusate and liver and between liver and bile. In both cases, distribution toward the liver is favored.