Melissa Mariana

The effects of phthalates in the cardiovascular and reproductive systems: A review.

Every year millions of tons of plastic are produced around the world and humans are increasingly exposed to them. This constant exposure to plastics has raised some concerns against human health, particularly when it comes to phthalates. These compounds have endocrine-disrupting properties, as they have the ability to bind molecular targets in the body and interfere with hormonal function and quantity. The main use of phthalates is to give flexibility to polyvinyl chloride (PVC) polymers. Phthalates are found in a variety of industrial and consumer products, and as they are not covalently bound to the plastic, phthalates contaminate the environment from which human exposure occurs. Studies in human and animal populations suggest a correlation between phthalate exposure and adverse health outcomes, particularly at the reproductive and cardiovascular systems, however there is much less information about the phthalate toxicity of the later. Thus, the main purpose of this review is to present the studies relating the effects already stated of phthalates on the cardiovascular and reproductive systems, and also present the link between these two systems.

Mifepristone is a Vasodilator Due to the Inhibition of Smooth Muscle Cells L-Type Ca2+ Channels

Derived from the estrane progestins, mifepristone was the first synthetic steroid of this class employed as abortifacient in the first months of pregnancy. Mifepristone reduces high potassium-induced contraction and prevents calcium-induced contraction. At the vascular level, mifepristone induces direct relaxation in rat and human arteries, and this effect seems to be endothelium- and NO independent, suggesting that the vascular smooth muscle is its target. Moreover, mifepristone’s effect could involve the modulation of different calcium channels. The aim of the present study is to analyze the involvement of calcium channels in the relaxation induced by mifepristone on vascular smooth muscle cells (VSMCs). Planar cell surface area (PCSA) technique was used to analyze the effect of mifepristone on the VSMC contractility, and the whole cell configuration of patch-clamp technique to measure the activity of L-type Ca2+ channels (LTCC) in A7r5 cells. Regarding the PCSA technique, mifepristone induced relaxation of the VSMC previously contracted by different agents. Also, a rapid inhibitory effect on basal and BAY K8644-stimulated calcium current was observed, which indicates that this drug has the ability to block LTCC. These results suggest that mifepristone induces relaxation on the VSMCs due to the inhibition of the calcium channels.

Photoprotection of ultraviolet-B filters: Updated review of endocrine disrupting properties

Graphical abstract Figure. No caption available. HighlightsOctylmethoxycinnamate (OMC) is the most commonly used sunscreen (ultraviolet filter).OMC is an endocrine disrupting compound, since it deregulates hormonal homeostasis.OMC exerts an estrogenic, anti‐androgenic, anti‐progestenic and anti‐thyroid activity. ABSTRACT The Ultraviolet (UV) radiation is emitted by the sun and is part of the electromagnetic spectrum. There are three types of UV rays (UV‐A, UV‐B and UV‐C), however only UV‐A and UV‐B have biologic effects in humans, with UV‐B radiation being primarily responsible for these effects. Among the measures of photoprotection advised by the health authorities, the topical application of sunscreens (containing UV‐B filters) is the preferred worldwide. Currently, octylmethoxycinnamate (OMC) is the most commonly used UV‐B filter in sunscreens. Their application has proven to be effective in preventing burns, but its efficiency against melanoma continues under intense controversy. Studies have shown that OMC behaves like an endocrine disruptor, altering the normal functioning of organisms. However, few studies have evaluated their multiple hormonal activities. Some studies suggest that the OMC exerts an estrogenic, anti‐androgenic, anti‐progestenic and anti‐thyroid activity. But, through what mechanisms? In humans, few studies were performed, and some questions remain unclear. Thus, the purpose of this review is to present the multiple hormonal activities established for the OMC, making a critical analysis and relationship between the effects in cells, animals and humans.

Genomic and Nongenomic Effects of Mifepristone at the Cardiovascular Level: A Review:

Mifepristone (RU 486) is a compound that is structurally related to steroid hormones, which is derived from the estrane progestins. This compound strongly binds the progesterone and glucocorticoid receptor and, to a lesser extent, the androgen receptor. This compound has its effects through different signaling pathways, related to genomic and nongenomic effects. The genomic effect involves the activation or blockage of nuclear or intracellular receptor, that in this case the progesterone, glucocorticoid, and androgen receptors. On the contrary, the nongenomic effect of mifepristone is independent of the activation of these receptors. Regarding the nongenomic, several authors observed that mifepristone induces higher uterine artery blood flow probably due to the decrease in serum nitric oxide level. Moreover, recently it has been demonstrated that mifepristone induces relaxation, and this effect is independent of the endothelium and due to the activation of the calcium channels. The main side effects associated with this pathway are hemorrhage and inhibition of platelet aggregation that can lead to hypovolemia or to hypotension. Concerning the genomic effect, this drug blocks progesterone, androgens, and glucocorticoids receptors and also activates the progesterone receptor and their respective effects. The most frequently reported adverse effects of mifepristone are nausea, vomiting, hypovolemia, hypotension, amenorrhea, and infertility. The main purpose of this review is to describe the genomic and nongenomic effects of mifepristone at vascular level and describe some pathologies in which mifepristone is used as a treatment.

Inhibition of L-type calcium channels by Bisphenol A in rat aorta smooth muscle

Bisphenol A (BPA) is an endocrine disrupting chemical used on a wide range in industry. This compound has been used in the production of polycarbonate plastics and epoxy resins. For this reason and their global use, BPA is one of the most common environmental chemicals to which humans are exposed. This exposure can cause several adverse health outcomes, including at the cardiovascular level. The regulation of ion channels in vascular smooth muscle is pivotal and important for vasoreactivity, and changes in their flux can be involved in the pathophysiology of some cardiovascular diseases. This study aims to analyse in rat aorta whether the vasorelaxant effect of BPA is mediated by L-type Ca2+ channels inhibition. Using male Wistar rat aorta artery rings in the organ bath we analysed the contractility, and to study the activity of calcium current in A7r5 cells we used the whole cell configuration of Patch Clamp technique. Regarding the contractility experiences we observed that in both NA and KCl contraction, BPA caused a rapid and concentration-dependent relaxation. The electrophysiology experiments showed that BPA inhibited the basal and BAY K8644-stimulated whole-cell L-type Ca2+ channel (W-CLTCC) currents, indicating that this drug blocks the L-type Ca2+ channels. Our results suggest that BPA inhibits the W-CLTCC, leading to the relaxation of vascular smooth muscle.

How is the human umbilical artery regulated

The purpose of this review is to present an update of the main mechanisms involved in the physiological regulation of contraction and relaxation of the human umbilical artery (HUA) smooth muscle cells. A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the regulation of the HUA are presented in this article. The vascular smooth muscle is a highly specialized structure, whose main function is to regulate the vascular tonus. This is controlled by a balance between the cellular signaling pathways that mediate contraction and relaxation. The cells responsible for the contractile property of this muscle are the smooth muscle cells (SMC), and an excellent source of these cells is the HUA, involved in fetoplacental circulation. Since the umbilical blood vessels are not innervated, the HUA tonus is modulated by vasoactive substances that regulate the contractile process. The main vasoactive substances that induce contraction are serotonin, histamine, thromboxane, bradykinin, endothelin 1 and prostaglandin F2α, that are linked to the activation of proteins Gq and Gi/0. On the other hand, the main vasorelaxation mechanisms are the activation of adenyl and guanil cyclases, potassium channels and the inhibition of calcium channels. The SMC from the HUA allow the study of different cellular mechanisms and their functions. Therefore, these cells are an important tool to study the mechanisms regulating the contractility of this artery, allowing to detect potential therapeutic targets to treat HUA disorders (gestational hypertension and pre‐eclampsia).

Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal

Pre-eclampsia and eclampsia are two hypertensive disorders of pregnancy, considered major causes of maternal and perinatal death worldwide. Pre-eclampsia is a multisystemic disease characterized by the development of hypertension after 20 weeks of gestation, with the presence of proteinuria or, in its absence, of signs or symptoms indicative of target organ injury. Eclampsia represents the consequence of brain injuries caused by pre-eclampsia. The correct diagnosis and classification of the disease are essential, since the therapies for the mild and severe forms of pre-eclampsia are different. Thus, this review aims to describe the most advisable antepartum pharmacotherapy for pre-eclampsia and eclampsia applied in Portugal and based on several national and international available guidelines. Slow-release nifedipine is the most recommended drug for mild pre-eclampsia, and labetalol is the drug of choice for the severe form of the disease. Magnesium sulfate is used to prevent seizures caused by eclampsia. Corticosteroids are used for fetal lung maturation. Overall, the pharmacological prevention of these diseases is limited to low-dose aspirin, so it is important to establish the safest and most effective available treatment.

Tributyltin Affects Rat Vascular Contractility Through L-Type Calcium Channels

The humans being exposed to tributyltin (TBT), through the ingestion of contaminated diet, particularly seafood, and through the ingestion of indoor dust. TBT is one of the most studied organotins and some reports demonstrated that this compound interferes with the physiology of the cardiovascular system; however, the exact mechanisms involved are still under discussion. Hence, this study aims to evaluate the effects of TBT on the vascular function. The evaluation of TBT effects on the contractility of rat aorta was performed using the organ bath technique using two different contractile agents: noradrenaline (NA) and potassium chloride (KCl). The whole-cell configuration of the patch clamp technique was performed to evaluate the TBT effects on the calcium currents of A7r5 cell line. The results demonstrate that TBT interferes with the vascular system as it elicits relaxation of the rat aorta contracted by NA or by KCl and inhibits L-type calcium currents in smooth muscle cells.

Cardiovascular Response of Rat Aorta to Di-(2-ethylhexyl) Phthalate (DEHP) Exposure

Phthalates are one of the main constituents of plastic, reaching up to 40% of the total plastic weight, and their main function is to impart flexibility/elasticity to polymers that would otherwise be rigid. Phthalates are known as endocrine disruptors, since they can interfere with hormone homeostasis. Regarding the cardiovascular system, it was already shown the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure with significant changes in several calcium-handling proteins and an increase in the blood pressure of mice offspring, suggesting that DEHP leads to vasocontraction. However, the mechanisms involved were not elucidated yet. The aim of this study is to analyse the involvement of calcium channels in the effects induced by DEHP on vascular smooth muscle cells. Endothelium-denuded aorta artery rings were prepared from male Wistar rats and incubated in an organ bath, and the whole-cell configuration of Patch Clamp technique was used to measure the activity of L-type Ca2+ channels (LTCC) in A7r5 cells. Overall, DEHP caused relaxation on KCl-induced contraction at higher concentrations and inhibited the basal and BAY K8644-stimulated calcium current, indicating that this drug blocks LTCC. These results suggest that DEHP induces relaxation on vascular smooth muscle cells due to the inhibition of calcium channels.