Entrez PubMed Nucleotide Protein Genome Structure OMIM PMC Journals Books
 Search for
  Limits Preview/Index History Clipboard Details    
About Entrez
spacer gif
back to About Entrez
back to About Entrez

Text Version

Entrez PubMed
Help | FAQ

PubMed Services
Journals Database
MeSH Database
Single Citation Matcher
Batch Citation Matcher
Clinical Queries

Related Resources
Order Documents
NLM Gateway
Consumer Health
Clinical Alerts
PubMed Central

Privacy Policy


1: Gut. 2003 Feb;52(2):300-3. Related Articles, Links
Click here to read 
Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2).

Milkiewicz P, Chilton AP, Hubscher SG, Elias E.

Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK.

BACKGROUND: We report two cases of antidepressant induced cholestasis. Case reports: We describe the first reported case of acute cholestasis due to citalopram (selective serotonin reuptake inhibitor) occurring in a patient who also experienced obstetric cholestasis in association with each of three pregnancies; in a second patient cholestasis developed due to dothiepin (tricyclic antidepressant), and six years later due to paroxetine. In both cases liver biopsies showed features of a "pure" cholestasis with total resolution within 1-6 months after withdrawal of the causative drug. Immunostaining for the canalicular transporter, multidrug resistant protein 2 (MRP2), responsible for biliary secretion of several organic anions including bilirubin glucuronides, showed sustained expression in both biopsies as well as relocalisation with appearance of strong staining of the basolateral membrane of the hepatocyte. This finding has also not been reported previously. CONCLUSIONS: We postulate that intracellular redistribution of MRP2 may reflect an adaptive compensatory mechanism which helps in the elimination of the drug or its cholestatic metabolites from the hepatocyte back to the sinusoidal space and subsequent excretion in urine. Changes seen in these two patients differ from findings previously reported in rats where downregulation of mrp2 occurs in response to experimentally induced cholestasis. We speculate that the rat is more advanced than humans in its ability to downregulate canalicular transporter expression as protection against progressive intrahepatic cholestasis.

Publication Types:
  • Case Reports

PMID: 12524417 [PubMed - indexed for MEDLINE]