Targeted Metabolomics Analysis Suggests That Tacrolimus Alters Protection against Oxidative Stress.
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Targeted Metabolomics Analysis Suggests That Tacrolimus Alters Protection against Oxidative Stress
by Marie Joncquel
1 [ORCID] , Julie Labasque
1, Julie Demaret
2 [ORCID] , Marie-Adélaïde Bout
1, Aghilès Hamroun
3, Benjamin Hennart
4, Mathieu Tronchon
2, Magali Defevre
1, Isabelle Kim
1, Alain Kerckhove
1, Laurence George
1, Mylène Gilleron
1, Anne-Frédérique Dessein
1, Farid Zerimech
1,5 [ORCID] and Guillaume Grzych
1,*
1
CHU Lille, Centre de Biologie Pathologie Génétique, Service Hormonologie Métabolisme Nutrition Oncologie, F-59000 Lille, France
2
CHU Lille, Centre de Biologie Pathologie Génétique, Institut d’Immunologie, F-59000 Lille, France
3
UMR1167 RIDAGE, Institut Pasteur de Lille, Inserm, Université de Lille, CHU Lille, F-59000 Lille, France
4
CHU Lille, Centre de Biologie Pathologie Génétique, Service Toxicologie et Génopathies, F-59000 Lille, France
5
Institut Pasteur de Lille, Université de Lille, ULR 4483, IMPECS, F-59000 Lille, France
*
Author to whom correspondence should be addressed.
Antioxidants 2023, 12(7), 1412; https://doi.org/10.3390/antiox12071412
Submission received: 23 June 2023 / Revised: 6 July 2023 / Accepted: 11 July 2023 / Published: 12 July 2023
(This article belongs to the Special Issue Redox Biomarkers in Dietary Interventions and Nutritional Observation Studies)
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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.
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