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

PLoS One. 2020 Mar 31;15(3):e0230977. doi: 10.1371/journal.pone.0230977. eCollection 2020.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Ergothioneine / pharmacology*
  • Female
  • Metabolome / drug effects*
  • Perfusion
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Pressure
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Ergothioneine

Grant support

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.