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Effects of rifampicin on global gene expression in human small intestine

Mikael Oscarson1, Oliver Burk, Stefan Winter

  • 1Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, Basel, Switzerland.

Pharmacogenetics and Genomics
|December 14, 2007
PubMed
Abstract

Insights

Rifampicin alters gene expression in the small intestine, affecting drug metabolism and transport. In vivo studies revealed more changes than in vitro cell models, highlighting the complexity of drug responses in the gut.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Gastroenterology

Background:

  • The small intestine acts as a barrier against foreign substances, utilizing enzymes and transporters to manage xenobiotics.
  • Xenobiotic-induced transcriptional activation of these protective genes is well-documented in the liver but less understood in the intestine.

Purpose of the Study:

  • To investigate the effects of the inducer drug rifampicin on intestinal gene expression.
  • To compare in vivo and in vitro responses of intestinal cells to rifampicin exposure.

Main Methods:

  • Gene expression profiling of duodenal biopsies from healthy volunteers before and after 9-day rifampicin treatment.
  • Assessing gene expression in LS174T colon adenocarcinoma cells after 24-hour exposure to rifampicin.

Main Results:

  • Rifampicin upregulated 32 genes and downregulated 2 genes in vivo.
  • Affected genes included those involved in drug metabolism, transport, lipid, and amino acid metabolism.
  • A limited overlap was observed between in vivo and in vitro rifampicin-regulated transcripts.

Conclusions:

  • Rifampicin significantly impacts intestinal gene expression, influencing diverse metabolic and transport systems.
  • Comparing in vivo and in vitro models reveals differences in cellular response to drug exposure, offering insights into xenobiotic adaptation.

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