Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F19%3A50015602" target="_blank" >RIV/62690094:18470/19:50015602 - isvavai.cz</a>
Result on the web
<a href="http://www.eurekaselect.com/166794/article" target="_blank" >http://www.eurekaselect.com/166794/article</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1389200219666181031113505" target="_blank" >10.2174/1389200219666181031113505</a>
Alternative languages
Result language
angličtina
Original language name
Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity
Original language description
Background: Cyclosporine A (CsA) is widely used for organ transplantation and autoimmune disorders. However, CsA nephrotoxicity is a serious side effect that limits the clinical use of CsA. The metabolism of CsA has a close relationship with this disease in renal-transplant patients. However, the metabolic pathways of CsA and its metabolizing enzymes have rarely been comprehensively reviewed. In this review, we have summarized the specific metabolic profiles of CsA in humans, especially renal-transplant patients. Moreover, the specific metabolizing enzymes and the potential roles that CsA metabolism plays in CsA nephrotoxicity were summarized and discussed. Methods: Electronic databases including PubMed, Web of Science, and Scifinder were searched with the keywords "Cyclosporine A and metabolism", and "Cyclosporine A and nephrotoxicity", "Cyclosporine A metabolism and nephrotoxicity". All these studies published until 2018 were included in this review. Results: The major metabolic pathways of CsA in humans are hydroxylation and N-demethylation. Normally, these metabolites are relatively less toxic than CsA. However, the metabolism of CsA in the kidneys is much weaker than that in the liver, which explains why CsA is so toxic to the kidneys. CYP3A families, especially CYP3A4 and CYP3A5, play an important role in the biotransformation of CsA. Moreover, increased lines of evidence show that some metabolites (including AM19) associate directly with nephrotoxicity in CsA-treated organ-transplant patients. Conclusion: The findings of this review help to further understand the metabolic activities of CsA in renal-transplant patients and cast some light on the mechanisms of CsA nephrotoxicity.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Current drug metabolism
ISSN
1389-2002
e-ISSN
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Volume of the periodical
20
Issue of the periodical within the volume
2
Country of publishing house
AE - UNITED ARAB EMIRATES
Number of pages
7
Pages from-to
84-90
UT code for WoS article
000466293500001
EID of the result in the Scopus database
2-s2.0-85065789222