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Effect of L-Ergothioneine on the metabolic plasma profile of the RUPP rat model of preeclampsia

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posted on 07.05.2020, 10:31 by AC Morillon, RD Williamson, PN Baker, DB Kell, LC Kenny, JA English, FP McCarthy, C McCarthy
Introduction Pre-eclampsia is a major cause of maternal and fetal mortality and morbidity worldwide. Its pathophysiology remains unclear, but mitochondrial dysfunction and oxidative stress have been implicated. L-Ergothioneine is a naturally occurring, water-soluble betaine, that has demonstrated antioxidant properties. Using the reduced uterine perfusion pressure (RUPP) rat model of pre-eclampsia, this study aimed to define the plasma metabolic profile following treatment with L-Ergothioneine. Methods The effect of L-Ergothioneine (ET) treatment was explored using in vivo treatment in rats: Sham control (SC, n = 5), RUPP control (RC, n = 5), Sham +ET (ST, n = 5), RUPP +ET (RT, n = 5). Differential expression of plasma metabolites were obtained using untargeted liquid chromatography coupled to mass spectrometry. Statistical analysis was performed on normalised data comparing RC to SC, RT to RC, and RT to ST. Metabolites significantly altered (FDR < 0.05) were identified through database search. Results We report significantly lower levels of L-palmitoylcarnitine in RC compared to SC, a fatty acyl substrate involved in beta-oxidation in the mitochondria. We report that a metabolite that has been associated with oxidative stress (Glutamylcysteine) was detected at significantly higher levels in RT vs RC and RT vs ST. Five metabolites associated with inflammation were significantly lower in RT vs RC and three metabolites in RT vs ST, demonstrating the anti-inflammatory effects of ET in the RUPP rat model of pre-eclampsia. Conclusions L-Ergothioneine may help preserve mitochondrial function by increasing antioxidant levels, and reducing inflammatory responses associated with pre-eclampsia. This study shows the potential of L-Ergothioneine as a treatment for pre-eclampsia.

Funding

ACM was funded by a Science Foundation Ireland (https://www.sfi.ie/) (12/RC/2272), and CM and RDW are funded through Health Research Board Ireland (https://www.hrb.ie/), (HRA-POR-2015-1240). JAE is funded by Health Research Board Ireland HRB EIA-2017-023. DBK thanks the BBSRC and the Novo Nordisk Foundation (https://novonordiskfonden.dk/en/) (grant NNF10CC1016517) for financial support. Waters Corporation provided access to mass spectrometry instrumentation (https://www.waters.com/nextgen/us/en.html?locale=en_GB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

History

Citation

Morillon A-C, Williamson RD, Baker PN, Kell DB, Kenny LC, English JA, et al. (2020) Effect of L-Ergothioneine on the metabolic plasma profile of the RUPP rat model of pre-eclampsia. PLoS ONE 15(3): e0230977. https://doi.org/10.1371/journal.pone.0230977

Published in

PLoS ONE

Volume

15

Issue

3

Pagination

e0230977

Publisher

Public Library of Science (PLoS)

issn

1932-6203

eissn

1932-6203

Acceptance date

12/03/2020

Copyright date

2020

Available date

31/03/2020

Publisher version

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230977

Language

eng