Antioxidants as stabilizers of UV filters: an example for the UV-B filter octylmethoxycinnamate

Background: Sunlight is one of the main harmful exogenous factors that induce the reactive oxygen species formation. The human skin is the first line of photoprotection against harmful exogenous factors, such as UV radiations. The topical application of sunscreens, containing UV-B filters, is widely used to protect against UV-induced damage. Octylmethoxycinnamate is the world’s most widely used UV-B filter in sunscreens. However, recent studies have demonstrated that this substance is an endocrine disruptor compound and with potential to damage DNA. Thus, the safety of this organic filter is a current concern for human health, and it was urgent to develop new photoprotective strategies. In this sense, due to the potential to neutralize the UV-induced free radicals, the use of antioxidants as UV filter stabilizers presented as a novel promising strategy. Research: The purpose of this review was to assess the use of antioxidants as stabilizers for UV-B filter octylmethoxycinnamate. For this, we discuss the chemical and physical characteristics of UV-B filter octylmethoxycinnamate, emphasizing the stability, photostability, and reactivity of this UV filter. The use of antioxidants in sunscreens will also be addressed, from a perspective of the main characteristics that allowed their use in sunscreen formulations. Then, the concomitant use of both was described from a historical and physical chemical perspective, always emphasizing the advantages and disadvantages of this association. Conclusions: The combination of antioxidants with UV-B filter octylmethoxycinnamate in appropriated formulations represents a viable strategy to protect the human skin against UV-induced damage.UBI-Santander Totta (BID/FCS/2018)info:eu-repo/semantics/publishedVersio

Efeitos genómicos do octilmetoxicinamato (OMC) a nível vascular

A aplicação tópica de protetores solares contra os efeitos nocivos da radiação ultravioleta é a proteção preferida a nível mundial. Atualmente, o octilmetoxicinamato (OMC) é um dos filtros ultravioleta-B mais utilizado na composição dos protetores solares. Estudos recentes demostraram que o OMC pode comportar-se como um disruptor endócrino, mas a nível vascular apenas um estudo inicou a avaliação dos seus efeitos. Neste sentido, o objetivo geral do presente trabalho consistiu no estudo do efeito do OMC no tónus arterial e na análise dos possíveis mecanismos envolvidos neste efeito. Para atingir este objetivo foram delineados os seguintes objetivos específicos: 1) Realizar com sucesso o isolamento e cultura de células musculares lisas da artéria umbilical humana (HUASMC); 2) Analisar o efeito do OMC em artérias umbilicais humanas (HUA) sem endotélio, e em HUASMC; 3) Analisar possíveis mecanismos envolvidos no efeito do OMC em HUA, principalmente o envolvimento dos nucleótidos cíclicos e dos canais de cálcio. Os resultados demonstraram que o OMC exerce um efeito relaxante arterial rápido (não genómico) e independente de endotélio. Também provoca relaxamento a nível das HUASMC. O mecanismo de ação do OMC pode ser, em parte, semelhante ao dos estrogénios, envolvendo a ativação da guanil ciclase solúvel, com aumento dos níveis de cGMP. Para além disso, este mecanismo não envolve a ativação dos canais de cálcio do tipo L. Estudos adicionais são necessários para compreender melhor o mecanismo de ação do OMC a nível vascular.The topical application of sunscreens against the harmful effects of ultraviolet radiation is the preferred protection worldwide. Octylmethoxycinnamate (OMC) is one the most widely used ultraviolet-B filter in the composition of sunscreens. Recent studies have shown that the OMC behaves like an endocrine disruptor, but at vascular level only one study initiated the evaluation of its effects. In this sense, the aim of the present study was to investigate the effect of the OMC on the arterial tonus and the analysis of the possible mechanisms involved in this effect. To achieve this prupose, specific objectives were outlined: 1) To perform the isolation and culture of the human umbilical artery smooth muscle cells (HUASMC); 2) To analyse the effect of the OMC in human umbilical arteries (HUA) without endothelium, and in HUASMC; 3) To analyse the mechanism involved in the OMC effect on HUA, mainly the involvement of cyclic nucleotides and calcium channels. Our results demonstrated that the OMC exerts a rapid (non-genomic) relaxing arterial effect and independent of endothelium. It also causes a relaxation at HUASMC level. The mechanism of action of the OMC can be, in part, similar to that of oestrogens, involving the activation of soluble guanyl cyclase, with increase of the cGMP levels. In addition, it does not go through an activation of the L-type calcium channels. Further studies are needed to better understand the mechanism of action of the OMC at vascular level

Vascular Pathways of Testosterone: Clinical Implications

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Testosterone (T) is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men. At the vascular level, the key effect of T is the vasorelaxation. This review discusses the molecular pathways and clinical implications of T in the vascular system. Firstly, the mechanisms involved in the T vasodilator effect will be presented. Then, it will be discussed the association of T with the main risks for CVD, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia and hypertension. Several studies have shown a correlation between low T levels and an increased prevalence of several CVD. These observations suggest that T has beneficial effects on the cardiovascular system and that testosterone replacement therapy may become a therapeutic reality for some of these disorders.UBI-Santander Totta (BID/FCS/2018)info:eu-repo/semantics/publishedVersio

Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)

Metformin is the most used oral anti-diabetic drug in the world and consequently is commonly found in the aquatic environment. Some studies demonstrated that metformin may act as an endocrine-disrupting-chemical (EDC) in fish, although it does not have a classic EDC structure. In this sense, the aim of this work was to evaluate the potential disrupting effect of metformin in the cardiovascular system through in vitro, ex vivo, and in silico studies. For this purpose, human umbilical artery (HUA) and rat aorta artery (RAA) were used. The toxic concentrations of metformin were determined by a cytotoxicity assay and in silico simulations were performed to analyze the interactions of metformin with hormonal receptors. Our results show that metformin decreases viability of the smooth muscle cells. Moreover, metformin induces a vasorelaxant effect in rat aorta and human models by an endothelium-dependent and -independent pathways. Furthermore, docking simulations showed that metformin binds to androgen receptors (AR) and estrogen receptors (ERα and ERβ). In conclusion, the in silico assays suggested that metformin has the potential to be an endocrine disruptor, acting mainly on ERα. Further studies are needed to use metformin in pregnant women without impairing the cardiovascular health of the future generation

PDE-Mediated Cyclic Nucleotide Compartmentation in Vascular Smooth Muscle Cells: From Basic to a Clinical Perspective

Cardiovascular diseases are important causes of mortality and morbidity worldwide. Vascular smooth muscle cells (SMCs) are major components of blood vessels and are involved in physiologic and pathophysiologic conditions. In healthy vessels, vascular SMCs contribute to vasotone and regulate blood flow by cyclic nucleotide intracellular pathways. However, vascular SMCs lose their contractile phenotype under pathological conditions and alter contractility or signalling mechanisms, including cyclic nucleotide compartmentation. In the present review, we focus on compartmentalized signaling of cyclic nucleotides in vascular smooth muscle. A deeper understanding of these mechanisms clarifies the most relevant axes for the regulation of vascular tone. Furthermore, this allows the detection of possible changes associated with pathological processes, which may be of help for the discovery of novel drugs

Clinical Importance of the Human Umbilical Artery Potassium Channels

Potassium (K+) channels are usually predominant in the membranes of vascular smooth muscle cells (SMCs). These channels play an important role in regulating the membrane potential and vessel contractility—a role that depends on the vascular bed. Thus, the activity of K+ channels represents one of the main mechanisms regulating the vascular tone in physiological and pathophysiological conditions. Briefly, the activation of K+ channels in SMC leads to hyperpolarization and vasorelaxation, while its inhibition induces depolarization and consequent vascular contraction. Currently, there are four different types of K+ channels described in SMCs: voltage-dependent K+ (KV) channels, calcium-activated K+ (KCa) channels, inward rectifier K+ (Kir) channels, and 2-pore domain K+ (K2P) channels. Due to the fundamental role of K+ channels in excitable cells, these channels are promising therapeutic targets in clinical practice. Therefore, this review discusses the basic properties of the various types of K+ channels, including structure, cellular mechanisms that regulate their activity, and new advances in the development of activators and blockers of these channels. The vascular functions of these channels will be discussed with a focus on vascular SMCs of the human umbilical artery. Then, the clinical importance of K+ channels in the treatment and prevention of cardiovascular diseases during pregnancy, such as gestational hypertension and preeclampsia, will be explored

Endocrine-Disrupting Effects of Bisphenol A on the Cardiovascular System: A Review

Currently, the plastic monomer and plasticizer bisphenol A (BPA) is one of the most widely used chemicals. BPA is present in polycarbonate plastics and epoxy resins, commonly used in food storage and industrial or medical products. However, the use of this synthetic compound is a growing concern, as BPA is an endocrine-disrupting compound and can bind mainly to estrogen receptors, interfering with different functions at the cardiovascular level. Several studies have investigated the disruptive effects of BPA; however, its cardiotoxicity remains unclear. Therefore, this review’s purpose is to address the most recent studies on the implications of BPA on the cardiovascular system. Our findings suggest that BPA impairs cardiac excitability through intracellular mechanisms, involving the inhibition of the main ion channels, changes in Ca2+ handling, the induction of oxidative stress, and epigenetic modifications. Our data support that BPA exposure increases the risk of developing cardiovascular diseases (CVDs) including atherosclerosis and its risk factors such as hypertension and diabetes. Furthermore, BPA exposure is also particularly harmful in pregnancy, promoting the development of hypertensive disorders during pregnancy. In summary, BPA exposure compromises human health, promoting the development and progression of CVDs and risk factors. Further studies are needed to clarify the human health effects of BPA-induced cardiotoxicity

UV-B Filter Octylmethoxycinnamate Alters the Vascular Contractility Patterns in Pregnant Women with Hypothyroidism

Increasing evidence relating the exposure and/or bioaccumulation of endocrine-disrupting compounds (EDCs) with cardiovascular system are arising. Octylmethoxycinnamate (OMC) is the most widely used UV-B filter and as EDC interacts with TH receptors. However, their effects on thyroid diseases during pregnancy remain unknown. The purpose of this work was to assess the short- and long-term effects of OMC on arterial tonus of pregnant women with hypothyroidism. To elucidate this, human umbilical artery (HUA) rings without endothelium were used to explore the vascular effects of OMC by arterial and cellular experiments. The binding energy and the modes of interaction of the OMC into the active center of the TSHR and THRα were analyzed by molecular docking studies. Our results indicated that OMC altered the contractility patterns of HUA contracted with serotonin, histamine and KCl, possibly due to an interference with serotonin and histamine receptors or an involvement of the Ca2+ channels. The molecular docking analysis show that OMC compete with T3 for the binding center of THRα. Taken together, these findings pointed out to alterations in HUA reactivity as result of OMC-exposure, which may be involved in the development and increased risk of cardiovascular diseases

UV-B Filter Octylmethoxycinnamate Is a Modulator of the Serotonin and Histamine Receptors in Human Umbilical Arteries

Every day, people use personal care products containing UV filters. Although their use initially showed a protective role, toxicity is a concern for human health as several UV filters are endocrine-disrupting chemicals (EDCs). Exposure to EDCs may induce cardiovascular diseases and can affect the health of sensitive people, such as pregnant women. Currently, the world’s most widely used UV-B filter is octylmethoxycinnamate (OMC), an EDC. However, the disruptive effects on pregnant women are little known. The present work proposed to understand how long-term exposure to OMC affects vascular homeostasis. Endothelium-denuded human umbilical artery (HUA) rings were incubated in an organ bath system. Long-term effects of exposure to OMC (0.001–50 μmol/L) were evaluated on the contractile responses of HUA to the application of the contractile agents, serotonin (5-HT) and histamine (Hist). To investigate in more detail the vascular mode of action of OMC, through which it impairs the vascular homeostasis of HUA, the activity and expression of different 5-HT and Hist-receptors involved in contractility processes were studied. Our findings pointed out an increase in the reactivity of HUA to 5-HT and Hist due to OMC exposure. These alterations in reactivity may be precursors of preeclampsia development and/or gestational hypertension

Vascular mechanisms of testosterone: the non-genomic point of view

Testosterone (T) is the predominant endogenous androgen in the bloodstream. At the vascular level, T presents genomic and non-genomic effects, and both effects may overlap. The genomic actions assume that androgens can freely cross the plasma membrane of target cells and bind to nuclear androgen receptors, inducing gene transcription and protein synthesis. The non-genomic effects have a more rapid onset and may be related to the interaction with protein/receptor/ion channels of the plasma membrane. The key T effect at the vascular level is vasorelaxation, which is primarily due to its rapid effect. Thus, the main purpose of this review is to discuss the T non-genomic effects at the vascular level and the molecular pathways involved in its vasodilator effect observed in in vivo and in vitro studies. In this sense, the nuclear receptor activation, the influence of vascular endothelium and the activation or inhibition of ion channels (potassium and calcium channels, respectively) will be reviewed regarding all the data that corroborated or not. Moreover, this review also provides a brief update on the association of T with the risk factors for cardiovascular diseases, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia, and hypertension. In summary, in this paper we consider the non-genomic vascular mode of action of androgen in physiological conditions and the main risk factors for cardiovascular diseases.info:eu-repo/semantics/publishedVersio