Effect of L-Ergothioneine on the metabolic plasma profile of the RUPP rat model of pre-eclampsia.,PLOS ONE

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Effect of L-Ergothioneine on the metabolic plasma profile of the RUPP rat model of pre-eclampsia.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-03-31 , DOI: 10.1371/journal.pone.0230977
Aude-Claire Morillon _{1,

2} , Rachel D Williamson ₁ , Philip N Baker ₃ , Douglas B Kell _{4,

5} , Louise C Kenny ₆ , Jane A English _{1,

7} , Fergus P McCarthy _{1,

2} , Cathal McCarthy ₈

Affiliation

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.

中文翻译：

L-麦角硫因对先兆子痫 RUPP 大鼠模型血浆代谢谱的影响。

介绍

先兆子痫是全世界孕产妇和胎儿死亡和发病的主要原因。其病理生理学尚不清楚，但与线粒体功能障碍和氧化应激有关。L-麦角硫因是一种天然存在的水溶性甜菜碱，具有抗氧化特性。本研究使用先兆子痫的子宫灌注压降低 (RUPP) 大鼠模型，旨在确定 L-麦角硫因治疗后的血浆代谢特征。

方法

使用大鼠体内治疗探索 L-麦角硫因 (ET) 治疗的效果：假手术对照 (SC, n = 5)、RUPP 对照 (RC, n = 5)、假手术 + ET (ST, n = 5)、 RUPP + ET（RT，n = 5）。使用非靶向液相色谱与质谱联用获得血浆代谢物的差异表达。对比较 RC 与 SC、RT 与 RC、RT 与 ST 的标准化数据进行统计分析。通过数据库搜索鉴定出显着改变的代谢物（FDR < 0.05）。

结果

我们报告，与 SC 相比，RC 中的 L-棕榈酰肉碱水平显着降低，L-棕榈酰肉碱是一种参与线粒体 β 氧化的脂肪酰基底物。我们报告说，在 RT 与 RC 以及 RT 与 ST 中检测到的与氧化应激相关的代谢物（谷氨酰半胱氨酸）的水平显着较高。与炎症相关的五种代谢物在 RT 中显着低于 RC，三种代谢物在 RT 中显着低于 ST，这证明了 ET 在先兆子痫的 RUPP 大鼠模型中的抗炎作用。