Document Detail


A possible explanation for anemia in patients treated with mycophenolic acid.
MedLine Citation:
PMID:  22075530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Clinical studies suggest that the immunosuppressant mycophenolate mofetil is associated with anemia. However, the mechanism for this is not known. Here, we studied the effect of mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, on erythropoiesis in vitro.
METHODS: Both UT-7 cells and primary murine bone marrow cells were studied. Cells were initially treated with erythropoietin and MPA and proliferation and caspase-3 assays were performed. The effect of guanosine-5'-triphosphate, guanosine, and caspase inhibitors was also investigated.
RESULTS: MPA was found to decrease the proliferation of UT-7 cells and erythropoiesis in murine bone marrow cells. This inhibition was associated with an increase in caspase-3 activity in the UT-7 cells. Inhibition was reversed in UT-7 cells and in murine bone marrow by guanosine, but not by caspase inhibitors. The apoptosis induced by MPA was also reversed by guanosine. UT-7 cells treated with MPA showed a decreased inosine-5'-monophosphate dehydrogenase activity.
CONCLUSION: These results suggest that MPA inhibits inosine-5'-monophosphate dehydrogenase activity in erythroid cells and that this is a likely mechanism of action of anemia in MPA-treated patients.
Authors:
Taryn Pile; Julius Kieswich; Steven Harwood; Muhammad M Yaqoob
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  92     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-14     Completed Date:  2012-03-20     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1316-21     Citation Subset:  IM    
Affiliation:
William Harvey Research Institute, Queen Mary, University of London, London, UK. teeps_tp@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Anemia / blood,  chemically induced,  pathology
Animals
Bone Marrow Cells / cytology,  drug effects
Caspase 3 / analysis
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Enzyme Inhibitors / adverse effects*,  metabolism
Erythropoietin / pharmacology
Female
Hematopoiesis / drug effects*
Humans
IMP Dehydrogenase / antagonists & inhibitors*
Mice
Mycophenolic Acid / adverse effects*,  analogs & derivatives,  metabolism
Young Adult
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 11096-26-7/Erythropoietin; 24280-93-1/Mycophenolic Acid; 9242ECW6R0/mycophenolate mofetil; EC 1.1.1.205/IMP Dehydrogenase; EC 3.4.22.-/Caspase 3

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


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