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In vitro induction of bilirubin conjugation in primary rat hepatocyte culture. | LitMetric

AI Article Synopsis

  • UGT1A1 is a key enzyme for breaking down bilirubin, and this study looked at how certain compounds affect its activity in rat liver cell cultures.
  • Hepatocytes initially showed a significant decrease in UGT1A1 activity after being cultured for 4 hours, but they gradually recovered over 72 hours, which was linked to a reduction in the enzyme's protein levels.
  • Treatment with dexamethasone, clofibrate, and rifampicin significantly boosted both UGT1A1 activity and protein levels, while methylcholanthrene had no effect on bilirubin conjugation.

Article Abstract

UDP-glucuronosyltransferase (UGT1A1) is a critical enzyme in the elimination of bilirubin. The aim of our study was to investigate bilirubin conjugation in primary rat hepatocyte culture and the in vitro inducibility of this isoenzyme by inducing compounds of different classes: dexamethasone, clofibrate, rifampicin, and methylcholanthrene. Hepatocytes exhibited a marked decline in UGT1A1 activity in the first 4 h of culturing (10% of initial activity) and the recovery took 72 h. Immunoblot analysis proved that the loss of enzyme activity was associated with the decrease of protein concentration. Marked induction was detected in the cases of dexamethasone, clofibrate, and rifampicin treatments for 96 h both in enzyme activity (178, 176, and 168%) and in UGT1A1 protein level (362, 328, and 250%). The effects of dexamethasone and clofibrate were additive (210%). Methylcholanthrene had no influence on bilirubin conjugation in our system.

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Source
http://dx.doi.org/10.1006/bbrc.2002.6400DOI Listing

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