Document Detail


Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2).
MedLine Citation:
PMID:  12524417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
P Milkiewicz; A P Chilton; S G Hubscher; E Elias
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  Gut     Volume:  52     ISSN:  0017-5749     ISO Abbreviation:  Gut     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-01-13     Completed Date:  2003-03-03     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  300-3     Citation Subset:  AIM; IM    
Affiliation:
Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adult
Antidepressive Agents / adverse effects*
Antidepressive Agents, Second-Generation / adverse effects
Antidepressive Agents, Tricyclic / adverse effects
Biopsy
Cholestasis / chemically induced*,  metabolism,  pathology
Citalopram / adverse effects
Dothiepin / adverse effects
Female
Humans
Immunohistochemistry
Liver / pathology
Male
Middle Aged
Mitochondrial Proteins*
Paroxetine / adverse effects
Pregnancy
Pregnancy Complications / chemically induced,  metabolism,  pathology
Ribosomal Proteins / metabolism*
Saccharomyces cerevisiae Proteins*
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Antidepressive Agents, Second-Generation; 0/Antidepressive Agents, Tricyclic; 0/MRP2 protein, S cerevisiae; 0/Mitochondrial Proteins; 0/Ribosomal Proteins; 0/Saccharomyces cerevisiae Proteins; 113-53-1/Dothiepin; 59729-33-8/Citalopram; 61869-08-7/Paroxetine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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