Mercury induces nuclear estrogen receptors to act as vasoconstrictors promoting endothelial denudation via the PI3K/Akt signaling pathway

Cordeiro, Evellyn Rodrigues; Filetti, Filipe Martinuzo; Vassallo, Dalton Valentim

doi:10.1016/j.taap.2019.114710

Cited by 8 publications

(2 citation statements)

References 83 publications

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“…69 Recently, a study from our group showed that in female rat aortas, acute exposure of mercury chloride increases vascular reactivity and induces oestrogen receptors to increase vasoconstriction. 70 Interestingly, when we blocked the oestrogen receptors ERα/ERβ with ICI 182780 and GPER with G-36 or when we stimulated GPER with G-1 in aortic rings from female rats exposed to mercury chloride, no alteration was observed in vascular reactivity to Phe. Likely, these vasoconstrictor effects found in acute exposure are compensated by some adaptive mechanisms during the 30 days of exposure, and no changes are observed in oestrogen receptors in our study.…”

Section: Discussionmentioning

confidence: 93%

Chronic mercury exposure induces oxidative stress in female rats by endothelial nitric oxide synthase uncoupling and cyclooxygenase‐2 activation, without affecting oestrogen receptor function

Schereider

Vassallo

2021

Basic Clin Pharma Tox

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Mercury has been shown to be a significant health risk factor and is positively associated with cardiovascular diseases. Evidence reveals that men are more likely to develop cardiovascular diseases than women during reproductive age.However, the effects of mercury in females remain poorly investigated, despite the finding that female hormones demonstrate a cardioprotective role. In the present study, we evaluated whether chronic mercury chloride exposure could alter blood pressure and vascular function of the female rat aorta.Ten-week-old female Wistar rats were divided into two groups: control (vehicle) and mercury treated (first dose of 4.6 μg/kg, subsequent daily doses of 0.07 μg/kg), im. Mercury treatment did not modify systolic blood pressure (SBP) but increased vascular reactivity due to the reduction of nitric oxide bioavailability associated with the increase in reactive oxygen species from endothelial nitric oxide synthase (eNOS) uncoupling. Furthermore, increased participation of the cyclooxygenase-2 pathway occurred through an imbalance in thromboxane 2 and prostacyclin 2. However, the oestrogen signalling pathway was not altered in either group. These results demonstrated that chronic exposure to mercury in females induced endothelial dysfunction and, consequently, increased aortic vascular reactivity, causing vascular damage to the female rat aorta and representing a risk of cardiovascular diseases.endothelial dysfunction, eNOS uncoupling, female rats, mercury chloride, vascular reactivity | INTRODUCTIONMercury has been recognized by the Agency for Toxic Substances and Disease Registry 1 as ranking third, behind arsenic and lead, on the priority list of substances that pose potential threats to human health due to its high toxicity and ability to biomagnify and bioaccumulate in the food chain. 2 Studies have shown that acute and chronic mercury exposure lead to adverse effects, such as the development of atherosclerosis, coronary artery disease, hypertension, changes in the oestrous cycle and features of polycystic ovary syndrome. [3][4][5][6][7]

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Section: Discussionmentioning

confidence: 93%

Chronic mercury exposure induces oxidative stress in female rats by endothelial nitric oxide synthase uncoupling and cyclooxygenase‐2 activation, without affecting oestrogen receptor function

Schereider

Vassallo

2021

Basic Clin Pharma Tox

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“…), was capable of damaging the architecture of the vascular endothelium, which may lead to the occurrence of vasculopathies. Previous studies have shown that both acute and chronic exposure to mercuric chloride (Cl2Hg) can also damage the endothelial layer of the aorta in Wistar females, exposing the internal elastic membrane of the vessel (Cordeiro et al 2019;Schereider et al 2021). Therefore, our ndings demonstrate that, like Hg, Cd is a metal that, even in in vitro exposures, is capable of damaging the structure of the vascular endothelium in females.…”

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confidence: 99%

In vitro cadmium exposure induces structural damage and endothelial dysfunction in female rat aorta

Sepulchro Mulher,

Simões,

Rossi

et al. 2023

Biometals

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Cadmium is a heavy metal that is widespread in the environment and has been described as a metalloestrogen and a cardiovascular risk factor. Experimental studies conducted in male animals have shown that cadmium exposure induces vascular dysfunction, which could lead to vasculopathies caused by this metal. However, it is necessary to investigate the vascular effects of cadmium in female rats to understand its potential gender-speci c impact on the cardiovascular system. While its effects on male rats have been studied, cadmium may act differently in females due to its potential as a metalloestrogen. In vitro studies conducted in a controlled environment allow for a direct assessment of cadmium's impact on vascular function, and the use of female rats ensures that gender-speci c effects are evaluated.Therefore, the aim of this study was to investigate the in vitro effects of Cadmium Chloride (ClCd2, 5µM) exposure on vascular reactivity in the isolated aorta of female Wistar rats. Exposure to ClCd2 damaged the architecture of the vascular endothelium. ClCd2 incubation increased the production and release of O2•-, reduced the participation of potassium (K+) channels, and increased the participation of the angiotensin II pathway in response to phenylephrine. Moreover, estrogen receptors alpha (Erα) modulated vascular reactivity to phenylephrine in the presence of cadmium, supporting the hypothesis that cadmium could act as a metalloestrogen. Our results demonstrated that in vitro cadmium exposure induces damage to endothelial architecture and an increase in oxidative stress in the isolated aorta of female rats, which could precipitate vasculopathies. INTRODUCTIONCadmium (Cd) is a non-essential metal that, in its ionic form, is considered a highly toxic element to the environment, as it has high transfer rates to the soil (ATSDR 2012; Satarug 2018). Cd is obtained from geogenic processes and anthropogenic sources, including the burning of fossil fuels, soil contamination from improper disposal of electronic waste, and the use of phosphate fertilizers (Jacobson and Turner 1980;Faroon O, Ashizawa A, Wright S 2012;Sripada and Lager 2022).Population exposure to Cd mainly occurs through soil and food contamination. Vegetables and tobacco leaves accumulate high levels of Cd from the soil, making them sources of contamination through consumption of contaminated food and inhalation of tobacco smoke (Hengstler et al. 2003;Satarug et al. 2003;ATSDR 2012). In fact, smokers have approximately three times the blood concentration of Cd compared to non-smokers (1.58 µg/L for smokers vs. 0.47 µg/L for non-smokers) (Abu-Hayyeh et al. 2001).Cd is an identi ed risk factor for cardiovascular diseases in humans (

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Combined exposure to multiple metals on abdominal aortic calcification: results from the NHANES study

Zhou,

Bai,

Zhao

2024

Environ Sci Pollut Res

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Mercury induces nuclear estrogen receptors to act as vasoconstrictors promoting endothelial denudation via the PI3K/Akt signaling pathway

Cited by 8 publications

References 83 publications

Chronic mercury exposure induces oxidative stress in female rats by endothelial nitric oxide synthase uncoupling and cyclooxygenase‐2 activation, without affecting oestrogen receptor function

Chronic mercury exposure induces oxidative stress in female rats by endothelial nitric oxide synthase uncoupling and cyclooxygenase‐2 activation, without affecting oestrogen receptor function

In vitro cadmium exposure induces structural damage and endothelial dysfunction in female rat aorta

Combined exposure to multiple metals on abdominal aortic calcification: results from the NHANES study

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