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

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.

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

“…A nutraceutical mitochondria-targeted antioxidant, L-ergothioneine (ERG), has also demonstrated potential therapeutic effects, particularly in PE ( 202 ). ERG is a water-soluble amino acid derived from histidine, which accumulates preferentially in high oxidative stress organs through the action of a specific organic cation transporter novel type 1 (OCTN1) ( 203 ).…”

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

“…Moreover, studies have suggested that ET is preferentially accumulated in tissues predisposed to oxidative stress and inflammation and may even be concentrated at sites of tissue injury by cellular modulation of the levels of OCTN1 [ 24 , 32 , 56 , 57 ]. These unique capabilities of ET, which have been reported in a wide range of studies in cells, animal models, and also population studies, suggest that the cytoprotective abilities of ET may be helpful against disorders such as dementia [ 58 , 59 , 60 ], depression [ 61 ], atherosclerosis [ 45 , 46 ], cardiovascular disorders [ 46 , 62 , 63 , 64 ], nonalcoholic fatty liver disease [ 56 ], preeclampsia [ 65 , 66 ], ischemia-reperfusion injury [ 39 , 50 , 67 ], and, especially relevant in this case, ARDS [ 68 ]. This list is by no means exhaustive, with new applications for ET constantly being identified even in other areas of human health, such as improving the efficacy of cancer vaccines [ 69 ] and protection against chemotherapy-induced peripheral neuropathy [ 70 ].…”

“…Studies have also suggested that ET is protective in preeclampsia, a hypertensive disorder during pregnancy that results in placental ischemia, by protecting against reperfusion-induced oxidative stress and inflammation, preserving mitochondrial function, and reducing hypertension in a reduced uterine perfusion pressure rat model of preeclampsia [ 65 , 66 , 154 ]. Conversely, mice deficient in OCTN1 (whose tissues are completely devoid of ET) are more susceptible to intestinal ischemia and reperfusion injury, with higher inflammatory markers and mortality compared with wild-type animals [ 101 ].…”

“…Based on present knowledge, the following diagram highlights how ET may protect various organs and tissues from oxidative damage and inflammatory injury amongst other cytoprotective effects in COVID-19 patients. The boxes in blue highlight systemic benefits for all tissues of the body [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 43 , 45 , 48 , 50 , 65 , 66 , 67 , 68 , 96 , 97 , 98 , 99 , 100 , 101 , 154 ].…”

Characterisation of Cardiac Health in the Reduced Uterine Perfusion Pressure Model and a 3D Cardiac Spheroid Model, of Preeclampsia

“…Pregnant rats were randomised to the Sham or RUPP procedure. At gestational day (GD) 14, the RUPP operation was performed as previously described [29,30]. Brie y, silver clips were applied to the aorta above the iliac bifurcation (0.203 mm ID) and both the right and left uterine arcades (0.100 mm ID) to reduce the blood ow to the uterus by ~ 40%.…”