Uptake of Glucuronides into Isolated Hepatocytes and their Effects on Glucuronide and Sulphate Conjugation

Abstract

Uptake studies, using radioactive labelled glucuronides, have demonstrated the ability of 4‐nitrophenyl glucuronide and phenolphthalein glucuronide to enter isolated rat hepatocytes. Of these glucuronides 4‐nitrophenyl glucuronide was distributed in a similar manner to O‐methylglucose, whereas phenolphthalein glucuronide was bound to cellular constituents. Phenolphthalein glucuronide had an effect on the conjugation of harmol in the isolated hepatocytes when glucuronidation was found to be markedly inhibited and sulphation slightly stimulated. The glucuronidation of 4‐nitrophenol, 4‐methylumbelliferone and harmol in native microsomes was inhibited by phenolphthalein glucuronide. 4‐Nitrophenyl glucuronide and also naphthyl glucuronide were without effect both in hepatocytes and microsomes. In control hepatocytes harmine was metabolized to form harmolsulphate mainly. Phenolphthalein glucuronide only affected this metabolic pattern to a minor extent. However, in hepatocytes from phenobarbital treated rats, where the rate of harmine metabolism is increased about five times and the main metabolite is harmol glucuronide, phenolphthalein glucuronide inhibited the formation of the conjugate with a concomitant increase in free harmol.

Disposition of flavonoids via recycling: Direct biliary excretion of enterically or extrahepatically derived flavonoid glucuronides

“…In 1978, Norling et al. showed that 4‐nitrophenyl glucuronide and phenolphthalein glucuronide were taken up by the hepatocytes. Studies published in the 1980s and 1990s, many by Vore and her coworkers, using primary hepatocytes have shown that hepatocytes are capable of taking up glucuronides of sex hormones (e.g., estradiol) , toxic bile acid lithocholate , diagnostic agent iopanoic acid , and certain drugs and other xenobiotics .…”

Glucuronide and Sulphate Binding to Subcellular Fractions of Rat Liver

“…There are differences in the binding of these metabolites to cellular constituents. Phenolphthaleinglucuronide which is excreted in bile in rats was bound but 4-nitrophenylglucuronide, excreted only in the urine, was not bound to the remnants of broken hepatocytes (Norling et a/. 1978a). In this work we have continued to further clarify the binding of glucuronides and sulphates to subcellular fractions of rat liver.…”