SARS- CoV-2 infection and oxidative stress in early-onset preeclampsia

SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) also in pregnant women. Infection in pregnancy leads to maternal and placental functional alterations. Pregnant women with vascular defects such as preeclampsia show high susceptibility to SARS-CoV-2 infection by undefined mechanisms. Pregnant women infected with SARS-CoV-2 show higher rates of preterm birth and caesarean delivery, and their placentas show signs of vasculopathy and inflammation. It is still unclear whether the foetus is affected by the maternal infection with this virus and whether maternal infection associates with postnatal affections. The SARS-CoV-2 infection causes oxidative stress and activation of the immune system leading to cytokine storm and next tissue damage as seen in the lung. The angiotensin-converting-enzyme 2 expression is determinant for these alterations in the lung. Since this enzyme is expressed in the human placenta, SARS-CoV-2 could infect the placenta tissue, although reported to be of low frequency compared with maternal lung tissue. Early-onset preeclampsia (eoPE) shows higher expression of ADAM17 (a disintegrin and metalloproteinase 17) causing an imbalanced renin-angiotensin system and endothelial dysfunction. A similar mechanism seems to potentially account for SARS-CoV-2 infection. This review highlights the potentially common characteristics of pregnant women with eoPE with those with COVID-19. A better understanding of the mechanisms of SARS-CoV-2 infection and its impact on the placenta function is determinant since eoPE/COVID-19 association may result in maternal metabolic alterations that might lead to a potential worsening of the foetal programming of diseases in the neonate, young, and adult

Can magnesium gluconate be used as an alternative therapy for preeclampsia?

Magnesium (Mg+2) in the body plays a structural and regulatory role and it is involved in fundamental cellular reactions. It is known that Mg+2 blood levels decrease during pregnancy, which has been related to preeclampsia and premature delivery, as well as other pathologies such as cardiovascular alterations and renal, gastrointestinal, neurological, and muscular dysfunctions among others. Mg+2 salts are used to treat its deficiency, and parenteral magnesium sulfate (MgSO4) is relatively effective in preeclampsia and eclampsia. The use of MgSO4 has the main disadvantage that it is mainly administered intravenously which leads to significant toxicity risks. Currently, other magnesium salts are being studied as alternative treatments. Magnesium gluconate (Mg-gluconate) has been used to prevent pregnancy-induced hypertension, showing a greater antioxidant capacity than MgSO4. Mg-gluconate can scavenge hydroxyl and alkoxyl radicals and it has been shown that it can inhibit lipid peroxidation in microsomal membranes treated in vitro with the Fenton reaction. Mg-gluconate seems to be an excellent candidate to replace MgSO4 as a therapy for preeclampsia with severe features.El magnesio (Mg+2) en el organismo, juega un papel estructural y regulador, y participa en reacciones celulares fundamentales. Se sabe que los niveles séricos de Mg+2 disminuyen durante el embarazo, lo cual se ha relacionado con la preeclampsia y el parto prematuro, así como con otras patologías como alteraciones cardiovasculares y disfunciones renales, gastrointestinales, neurológicas, musculares, entre otras. Las sales de Mg+2 se utilizan para tratar su deficiencia, y el sulfato de magnesio parenteral (MgSO4) ha demostrado ser relativamente eficaz en la preeclampsia y la eclampsia. El uso de MgSO4 tiene el principal inconveniente de que se administra principalmente por vía intravenosa, lo cual conlleva a riesgos importantes de toxicidad. Actualmente, se están estudiando otras sales de magnesio como tratamientos alternativos. El gluconato de magnesio (Mg-gluconato) se ha utilizado para prevenir la hipertensión inducida por el embarazo, mostrando una mayor capacidad antioxidante que el MgSO4. El Mg-gluconato es capaz de eliminar radicales hidroxilo y alcoxilo e inhibir la peroxidación lipídica en membranas microsomales tratadas in vitro con la reacción de Fenton. El Mg-gluconato parece ser un excelente candidato para sustituir al MgSO4 como terapia para la preeclampsia con características graves.Sociedad Argentina de Fisiologí

Oxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia

Preeclampsia is a pregnancy-specific syndrome with multisystem involvement which leads to foetal, neonatal, and maternal morbidity and mortality. This syndrome is characterized by the onset of clinical signs and symptoms and delivery before (early-onset preeclampsia, eoPE), or after (late-onset preeclampsia, loPE), the 34 weeks of gestation. Preeclampsia is a mitochondrial disorder where its differential involvement in eoPE and loPE is unclear. Mitochondria regulate cell metabolism and are a significant source of reactive oxygen species (ROS). The syncytiotrophoblast in eoPE and loPE show altered mitochondrial structure and function resulting in ROS overproduction, oxidative stress, and cell damage and death. Mitochondrial dysfunction in eoPE may result from altered expression of several molecules, including dynamin-related protein 1 and mitofusins, compared with loPE where these factors are either reduced or unaltered. Equally, mitochondrial fusion/fission dynamics seem differentially modulated in eoPE and loPE. It is unclear whether the electron transport chain and oxidative phosphorylation are differentially altered in these two subgroups of preeclampsia. However, the activity of complex IV (cytochrome c oxidase) and the expression of essential proteins involved in the electron transport chain are reduced, leading to lower oxidative phosphorylation and mitochondrial respiration in the preeclamptic placenta. Interventional studies in patients with preeclampsia using the coenzyme Q, a key molecule in the electron transport chain, suggest that agents that increase the antioxidative capacity of the placenta may be protective against preeclampsia development. In this review, the mitochondrial dysfunction in both eoPE and loPE is summarized. Therapeutic approaches are discussed in the context of contributing to the understanding of mitochondrial dysfunction in eoPE and loPE

Oxidative stress: Normal pregnancy versus preeclampsia.

The role of oxidative stress in the physiopathology of human pregnancy is of particular interest. Pregnancy is well-known to increase the oxidative stress, mainly produced by a normal systemic inflammatory response, which results in high amounts of circulating reactive oxygen species (ROS) and reactive nitrogen species (RNS). Both ROS and RNS play an important role as secondary messengers in many intracellular signalling cascades. However, they can also exert critical effects on pathological processes involving the pregnant woman. ROS, RNS and antioxidants establish a balance that determines the oxidation status of animals and humans. This review focuses on the mechanism of oxidative stress in pregnancy as well as its involvement and consequences on the human pregnancy-specific clinical syndrome preeclampsia

Oxidative stress: normal pregnancy versus preeclampsia

The role of oxidative stress in the physiopathology of human pregnancy is of particular interest. Pregnancy is well-known to increase the oxidative stress, mainly produced by a normal systemic inflammatory response, which results in high amounts of circulating reactive oxygen species (ROS) and reactive nitrogen species (RNS). Both ROS and RNS play an important role as secondary messengers in many intracellular signalling cascades. However, they can also exert critical effects on pathological processes involving the pregnant woman. ROS, RNS and antioxidants establish a balance that determines the oxidation status of animals and humans. This review focuses on the mechanism of oxidative stress in pregnancy as well as its involvement and consequences on the human pregnancy-specific clinical syndrome preeclampsia

Magnesium salts in pregnancy

Background: Magnesium is one of the most abundant elements in the body. Although the total serum magnesium content does not represent more than 1% of total body magnesium, serum magnesium determinations have been routinely used in clinical practice to assess body magnesium status. Thus, serum magnesium concentration ranges from 1.8 to 2.2 mg.dl−1 (0.75–0.95 mmol.l − 1 or 1.5–1.9 mEq.l − 1). Consequently, when serum magnesium levels fall below the range considered normal, the patient is diagnosed with hypomagnesemia. This deficiency has been associated with low-grade systemic inflammation, increased levels of proinflammatory molecules, mitochondrial dysfunction, increased reactive oxygen species production, and hypertriglyceridemia leading to an increase in the number of easily oxidizable lipoproteins in the circulation. Results: Several magnesium salts have been used to treat hypomagnesemia during pregnancy, with magnesium sulfate (MgSO4) being the most commonly used magnesium salt in current obstetric practice. However, the exact mechanism of action of MgSO4 remains largely an enigma, and its parenteral use poses a significant toxicological risk at high doses. In this review, we summarize the use of magnesium salts during pregnancy not only from a clinical point of view but also, with the use of computational simulations, discuss advances in the understanding of the molecular mechanisms of action of magnesium salts, with emphasis on MgSO4. These molecular simulations are required to unveil the pharmacological action of the magnesium salts during pregnancy. Conclusions: MgSO4 plays a role as an antioxidant agent at the plasma membrane level which can explain the mechanism of action of this salt in current obstetric practice