Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity

Popis výsledku v původním jazyce

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 &quot;Cyclosporine A and metabolism&quot;, and &quot;Cyclosporine A and nephrotoxicity&quot;, &quot;Cyclosporine A metabolism and nephrotoxicity&quot;. 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.

Název v anglickém jazyce

Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity

Popis výsledku anglicky

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 &quot;Cyclosporine A and metabolism&quot;, and &quot;Cyclosporine A and nephrotoxicity&quot;, &quot;Cyclosporine A metabolism and nephrotoxicity&quot;. 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Current drug metabolism

ISSN

1389-2002

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

7

Strana od-do

84-90

Kód UT WoS článku

000466293500001

EID výsledku v databázi Scopus

2-s2.0-85065789222