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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.

Preeclampsia (PE) is a pregnancy-specific syndrome with multisystem involvement which leads to fetal, neonatal, and maternal morbidity and mortality. A model of salt-loaded pregnant rats has been previously studied, sharing several pathological characteristics of preeclamptic women. In this study, it was compared the effects of the treatment with an oral magnesium salt, magnesium gluconate (Mg-gluconate), on the osmotic fragility of red blood cells, lipid peroxidation, and PMCA activity of placental homogenates and red blood cell ghosts in salt-loaded pregnant rats. Mg-gluconate has a higher antioxidant capacity than MgSO4 due to the presence of several hydroxyl groups in the two anions of this salt. Salt-loaded pregnant rats received 1.8% NaCl solution ad libitum as a beverage during the last week of pregnancy. On day 22nd of pregnancy, the rats were euthanized and red blood cells and placenta were obtained. Salt-loaded pregnant rats showed an increased level of lipid peroxidation and a lowered PMCA activity in placental and red blood cell ghosts, as well as an increased osmotic fragility of their red blood cells. The treatment of the salt-loaded pregnant rats with Mg-gluconate avoids the rise in the level of lipid peroxidation and the concomitant lowering of the PMCA activity of their red blood cell membranes, reaching values similar to those from control pregnant rats. Also, this treatment prevents the increase of the osmotic fragility of their red blood cells, keeping values similar to those from control pregnant rats. Mg-gluconate seems to be an important candidate for the replacement of the MgSO4 treatment of preeclamptic women.