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Effect of inflammation on molecular targets and drug transporters

Sherif Hanafy1, Ayman O S El-Kadi, Fakhreddin Jamali

  • 1Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.

Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques
|September 15, 2012
PubMed

Insights

Inflammation significantly alters gene expression of drug transporters in rat organs, impacting drug disposition and potentially leading to therapeutic failure. This study highlights key changes in liver, kidney, and heart transporter expression during chronic inflammation.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Immunology

Background:

  • Inflammation, a biological response to infection or injury, alters the expression of various genes, including those involved in drug metabolism and transport.
  • Understanding these alterations is crucial for predicting drug efficacy and managing potential therapeutic failures in inflammatory conditions.

Purpose of the Study:

  • To investigate the impact of chronic inflammation on the gene expression of specific drug transporters and molecular targets.
  • To characterize how inflammation affects drug action and disposition by examining changes in transporter expression in key organs.

Main Methods:

  • Utilized a rat model of adjuvant arthritis (AA) to induce chronic inflammation.
  • Quantified the gene expression of numerous drug transporters and inflammatory markers in heart, liver, kidneys, and intestine using real-time polymerase chain reaction (RT-PCR).

Main Results:

  • Significant downregulation of organic anion transporting polypeptide 4a1 (oatp4a1), organic cation transporter 1 (oct1), and multidrug resistance-associated protein 1 (mrp1) gene expression was observed in the liver.
  • Kidney exhibited significant reductions in oatp2b1, mrp6, and bile salt export pump (bsep) gene expression.
  • Oatp4a1 and multidrug resistance 1a (mdr1a) gene expression were significantly upregulated in the rat heart.

Conclusions:

  • Chronic inflammation demonstrably alters the gene expression profiles of critical drug transporters in various organs.
  • These changes in transporter expression can significantly influence drug pharmacokinetics and pharmacodynamics.
  • The observed alterations may contribute to reduced drug efficacy and therapeutic failure in patients with inflammatory diseases.

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