Document Detail

Biochemical mechanisms of cyclosporine neurotoxicity.
MedLine Citation:
PMID:  15087483     Owner:  NLM     Status:  MEDLINE    
Proper management of chemotoxicity in transplant patients requires detailed knowledge of the biochemical mechanisms underlying immunosuppressant toxicity. Neurotoxicity is one of the most significant clinical side effects of the immunosuppressive undecapeptide cyclosporine, occurring at some degree in up to 60% of transplant patients. The clinical symptoms of cyclosporine-mediated neurotoxicity consist of decreased responsiveness, hallucinations, delusions, seizures, cortical blindness, and stroke-like episodes that mimic those clinical symptoms of mitochondrial encephalopathy. Clinical computed tomography (CT) and magnetic resonance imaging (MRI) studies have revealed a correlation between clinical symptoms of cyclosporine-mediated neurotoxicity and morphological changes in the brain, such as hypodensity of white matter, cerebral edema, metabolic encephalopathy, and hypoxic damages. Paradoxically, in animal models cyclosporine protects the brain from ischemia-reperfusion (I/R) injury. Interestingly, cyclosporine appears to mediate both neurotoxicity (under normoxic conditions) and I/R protection across the same range of drug concentration. Both toxicity and protection might arise from the intersection of cyclosporine with mitochondrial energy metabolism. This review addresses basic biochemical mechanisms of: 1) cyclosporine toxicity in normoxic brain, and 2) its protective effects in the same organ during I/R. The marked and unparallel potential of magnetic resonance spectroscopy (MRS) as a novel quantitative approach to evaluate metabolic drug toxicity is described.
Natalie J Serkova; Uwe Christians; Leslie Z Benet
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Molecular interventions     Volume:  4     ISSN:  1543-2548     ISO Abbreviation:  Mol. Interv.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-16     Completed Date:  2008-03-24     Revised Date:  2009-06-22    
Medline Journal Info:
Nlm Unique ID:  101093789     Medline TA:  Mol Interv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  97-107     Citation Subset:  IM    
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
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MeSH Terms
Brain / metabolism
Cyclosporine / therapeutic use,  toxicity*
Energy Metabolism
Graft Rejection / drug therapy,  prevention & control
Hypoxia-Ischemia, Brain
Immunosuppressive Agents / therapeutic use,  toxicity*
Magnetic Resonance Spectroscopy
Mitochondrial Encephalomyopathies / physiopathology
Neurotoxicity Syndromes* / etiology,  physiopathology
Organ Transplantation
Grant Support
R01 DK065094-01/DK/NIDDK NIH HHS; R01 HL071805-01/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Immunosuppressive Agents; 59865-13-3/Cyclosporine

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