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Targeted Metabolomics Analysis Suggests That Tacrolimus Alters Protection against Oxidative Stress

Authors :
Marie Joncquel
Julie Labasque
Julie Demaret
Marie-Adélaïde Bout
Aghilès Hamroun
Benjamin Hennart
Mathieu Tronchon
Magali Defevre
Isabelle Kim
Alain Kerckhove
Laurence George
Mylène Gilleron
Anne-Frédérique Dessein
Farid Zerimech
Guillaume Grzych
Source :
Antioxidants, Vol 12, Iss 7, p 1412 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Tacrolimus (FK506) is an immunosuppressant that is experiencing a continuous rise in usage worldwide. The related side effects are known to be globally dose-dependent. Despite numerous studies on FK506, the mechanisms underlying FK506 toxicity are still not well understood. It is therefore essential to explore the toxicity mediated by FK506. To accomplish this, we conducted a targeted metabolomic analysis using LC−MS on the plasma samples of patients undergoing FK506 treatment. The aim was to identify any associated altered metabolic pathway. Another anti-calcineurin immunosuppressive therapy, ciclosporin (CSA), was also studied. Increased plasma concentrations of pipecolic acid (PA) and sarcosine, along with a decrease in the glycine/sarcosine ratio and a tendency of increased plasma lysine was observed in patients under FK506 compared to control samples. Patients under CSA do not show an increase in plasma PA compared to the control samples, which does not support a metabolic link between the calcineurin and PA. The metabolomics changes observed in patients under FK506 highlight a possible link between FK506 and the action of an enzyme involved in both PA and sarcosine catabolism and oxidative pathway, the Peroxisomal sarcosine oxidase (PIPOX). Moreover, PA could be investigated as a potential biomarker of early nephrotoxicity in the follow-up of patients under FK506.

Details

Language :
English
ISSN :
12071412 and 20763921
Volume :
12
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Antioxidants
Publication Type :
Academic Journal
Accession number :
edsdoj.984d6e22f4c44b10a8238bdd0ccb1327
Document Type :
article
Full Text :
https://doi.org/10.3390/antiox12071412