Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries

2008 ◽  
Vol 295 (3) ◽  
pp. H1033-H1043 ◽  
Author(s):  
G. A. Wiggers ◽  
F. M. Peçanha ◽  
A. M. Briones ◽  
J. V. Pérez-Girón ◽  
M. Miguel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Chronic Exposure ◽  
Total Antioxidant Status ◽  
Oxidase Inhibitor ◽  
Mercury Chloride ◽  
Blood Levels ◽  
Resistance Arteries ◽  
Low Concentrations ◽  
Underlying Mechanisms

Increased cardiovascular risk after mercury exposure has been described, but the underlying mechanisms are not well explored. We analyzed the effects of chronic exposure to low mercury concentrations on endothelium-dependent responses in aorta and mesenteric resistance arteries (MRA). Wistar rats were treated with mercury chloride (1st dose 4.6 μg/kg, subsequent dose 0.07 μg·kg−1·day−1im, 30 days) or vehicle. Blood levels at the end of treatment were 7.97 ± 0.59 ng/ml. Mercury treatment: 1) did not affect systolic blood pressure; 2) increased phenylephrine-induced vasoconstriction; 3) reduced acetylcholine-induced vasodilatation; and 4) reduced in aorta and abolished in MRA the increased phenylephrine responses induced by either endothelium removal or the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 μM). Superoxide dismutase (SOD, 150 U/ml) and the NADPH oxidase inhibitor apocynin (0.3 mM) decreased the phenylephrine-induced contraction in aorta more in mercury-treated rats than controls. In MRA, SOD did not affect phenylephrine responses; however, when coincubated with l-NAME, the l-NAME effect on phenylephrine response was restored in mercury-treated rats. Both apocynin and SOD restored the impaired acetylcholine-induced vasodilatation in vessels from treated rats. Endothelial NOS expression did not change in aorta but was increased in MRA from mercury-treated rats. Vascular O2−production, plasmatic malondialdehyde levels, and total antioxidant status increased with the mercury treatment. In conclusion, chronic exposure to low concentrations of mercury promotes endothelial dysfunction as a result of the decreased NO bioavailability induced by increases in oxidative stress. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.

Role of EGFR/ErbB2 and PI3K/AKT/e-NOS in Lycium barbarum polysaccharides Ameliorating Endothelial Dysfunction Induced by Oxidative Stress

2019 ◽  
Vol 47 (07) ◽  
pp. 1523-1539 ◽  
Author(s):  
Wenjuan Zhang ◽  
Huifang Yang ◽  
Lingqin Zhu ◽  
Yan Luo ◽  
Lihong Nie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Cell Viability ◽  
Therapeutic Option ◽  
Critical Role ◽  
Ang Ii ◽  
Lycium Barbarum ◽  
Underlying Mechanisms ◽  
Lycium Barbarum Polysaccharides

Lycium barbarum polysaccharides (LBP) are the major ingredients of wolfberry. In this study, we investigated the role of LBP in endothelial dysfunction induced by oxidative stress and the underlying mechanisms using thoracic aortic endothelial cells of rat (RAECs) as a model. We found that Ang II inhibits cell viability of RAECs with 10[Formula: see text][Formula: see text]mol/L of Ang II treatment for 24[Formula: see text]h most potential ([Formula: see text]), the level of reactive oxygen species (ROS) is increased by Ang II treatment ([Formula: see text]), and the expression of Occludin and Zonula occludens-1 (ZO-1) is decreased by Ang II treatment ([Formula: see text]). However, preincubation of cells with LBP could inhibit the changes caused by Ang II, LBP increased cell viability ([Formula: see text]), decreased the level of ROS ([Formula: see text]), and up-regulated the expression of Occludin ([Formula: see text]) and ZO-1. In addition, Ang II treatment increased the expression of EGFR and p-EGFR (Try1172) and which can be inhibited by LBP. On the contrary, expression of ErbB2, p-ErbB2 (Try1248), PI3K, p-e-NOS (Ser1177) ([Formula: see text]), and p-AKT (Ser473) ([Formula: see text]) was inhibited by Ang II treatment and which can be increased by LBP. Treatment of the cells with inhibitors showed that the regulation of p-e-NOS and p-AKT expression by Ang II and LBP can be blocked by PI3K inhibitor wortmannin but not EGFR and ErbB2 inhibitor AC480. Taken together, our results suggested that LBP plays a critical role in maintaining the integrality of blood vessel endothelium through reduced production of ROS via regulating the activity of EGFR, ErbB2, PI3K/AKT/e-NOS, and which may offer a novel therapeutic option in the management of endothelial dysfunction.

scholarly journals Hippocampal Dysfunction Provoked by Mercury Chloride Exposure: Evaluation of Cognitive Impairment, Oxidative Stress, Tissue Injury and Nature of Cell Death

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Walessa Alana Bragança Aragão ◽  
Francisco Bruno Teixeira ◽  
Nathalia Carolina Fernandes Fagundes ◽  
Rafael Monteiro Fernandes ◽  
Luanna Melo Pereira Fernandes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cognitive Impairment ◽  
Chronic Exposure ◽  
Tissue Injury ◽  
Cognitive Test ◽  
Exposure Model ◽  
Mercury Chloride ◽  
Low Doses ◽  
Hippocampal Dysfunction

Mercury (Hg) is a highly toxic metal, which can be found in its inorganic form in the environment. This form presents lower liposolubility and lower absorption in the body. In order to elucidate the possible toxicity of inorganic Hg in the hippocampus, we investigated the potential of low doses of mercury chloride (HgCl2) to promote hippocampal dysfunction by employing a chronic exposure model. For this, 56 rats were exposed to HgCl2 (0.375 mg/kg/day) via the oral route for 45 days. After the exposure period, the animals were submitted to the cognitive test of fear memory. The hippocampus was collected for the measurement of total Hg levels, analysis of oxidative stress, and evaluation of cytotoxicity, apoptosis, and tissue injury. It was observed that chronic exposure to inorganic Hg promotes an increase in mercury levels in this region and damage to short- and long-term memory. Furthermore, we found that this exposure model provoked oxidative stress, which led to cytotoxicity and cell death by apoptosis, affecting astrocytes and neurons in the hippocampus. Our study demonstrated that inorganic Hg, even with its low liposolubility, is able to produce deleterious effects in the central nervous system, resulting in cognitive impairment and hippocampal damage when administered for a long time at low doses in rats.

scholarly journals Parathyroid Hormone Causes Endothelial Dysfunction by Inducing Mitochondrial ROS and Specific Oxidative Signal Transduction Modifications

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Jessica Gambardella ◽  
Matteo De Rosa ◽  
Daniela Sorriento ◽  
Nella Prevete ◽  
Antonella Fiordelisi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mitochondrial Calcium ◽  
Calcium Fluxes ◽  
Mitochondrial Ros ◽  
Endothelial Response ◽  
Underlying Mechanisms

Vitamin D deficiency contributes to cardiovascular risk (CVR), with hyperparathyroidism advocated as a putative mechanism. Indeed, mounting evidence supports the hypothesis that parathyroid hormone (PTH) impairs endothelial function, even though mechanisms are not fully elucidated. The present study was designed to verify in vitro the ability of sustained exposure to PTH to cause endothelial dysfunction, exploring the underlying mechanisms. In bovine aortic endothelial cells (BAECs), we evaluated the effects of PTH exposure (0.1 nM–24 hours) on both endothelial response to vasodilators, such as bradykinin (Bk (30 nM)) and acetylcholine (Ach (1 μM)), and angiogenic competence. Pretreatment with PTH impaired endothelial response to Bk but not to Ach, in terms of cytosolic calcium fluxes and NO production. In order to explore the underlying mechanisms, we assessed the production of total and mitochondrial ROS (tROS and mROS, respectively) in response to PTH (at 1 and 3 hours). PTH increased ROS generation, to an extent high enough to determine oxidation of Bk receptor B2. Conversely, the oxidation levels of M1 and M3 Ach receptors were not affected by PTH. A mROS selective scavenger (MitoTEMPO (5 μM)) restored the endothelial responsiveness to Bk while the well-known antioxidant properties of vitamin D (100 nM) failed to counteract PTH-mediated oxidative stress. PTH determined mitochondrial calcium fluxes ([Ca2+]mt) and the mitochondrial calcium uniporter inhibitor Ru360 (10 μM) reduced mROS production and prevented the PTH-mediated endothelial dysfunction. Angiogenic competence was evaluated as tubular formations in the endothelial Matrigel assay and showed a significant impairment in PTH-pretreated cells (0.1 nM–24 hours), despite the increase in VEGF transcriptional levels. VEGFR2 oxidation occurred in response to PTH, suggesting that even the impairment of angiogenesis was due to the ROS surge. These results indicate that PTH affects endothelial function through ROS production, driven by mitochondrial calcium overload. PTH-induced oxidative stress might act as signaling modifiers, altering specific pathways (Bk and VEGF) and preserving others (Ach).

scholarly journals Role of oxidative stress in multiparity-induced endothelial dysfunction

2008 ◽  
Vol 295 (4) ◽  
pp. H1736-H1742 ◽  
Author(s):  
Huda E. Tawfik ◽  
Jonathan Cena ◽  
Richard Schulz ◽  
Susan Kaufman
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Coronary Arteries ◽  
Vascular Tissue ◽  
Fold Increase ◽  
Oxidase Inhibitor ◽  
Maximal Response ◽  
Protein Levels ◽  
Increased Risk

Multiparity is associated with increased risk of cardiovascular disease. We tested whether multiparity induces oxidative stress in rat vascular tissue. Coronary arteries and thoracic aorta were isolated from multiparous and age-matched virgin rats. Relaxation to ACh and sodium nitroprusside (SNP) was measured by wire myography. We also tested the effect of the superoxide dismutase mimetic MnTE2PyP (30 μM), the NADPH oxidase inhibitor apocynin (10 μM), and the peroxynitrite scavenger FeTPPs (10 μM) on ACh-mediated relaxation in coronary arteries. Vascular superoxide anion was measured using the luminol derivative L-012 and nitric oxide (NO) generation by the Griess reaction. Multiparity reduced maximal response and sensitivity to ACh in coronary arteries [maximal relaxation (Emax): multiparous 49 ± 3% vs. virgins 95% ± 3%; EC50: multiparous 135 ± 1 nM vs. virgins 60 ± 1 nM], and in aortic rings (Emax: multiparous 38 ± 3% vs. virgins 79 ± 4%; EC50: multiparous 160 ± 2 nM vs. virgins 90 ± 3 nM). Coronary arteries from the two groups relaxed similarly to SNP. Superoxide anions formation was significantly higher in both coronary arteries (2.8-fold increase) and aorta (4.1-fold increase) from multiparous rats compared with virgins. In multiparous rats, incubation with MnTE2PyP, apocynin, and FeTPPs improved maximal relaxation to ACh (MnTE2PyP: 74 ± 5%; vehicle: 41 ± 5%; apocynin: 73 ± 3% vs. vehicle: 41 ± 3%; FeTPPs: 72 ± 3% vs. vehicle: 46 ± 3%) and increased sensitivity (EC50: MnTE2PyP: 61 ± 0.5 nM vs. vehicle: 91 ± 1 nM; apocynin: 45 ± 3 nM vs. vehicle: 91 ± 6 nM; FeTPP: 131 ± 2 nM vs. vehicle: 185 ± 1 nM). Multiparity also reduced total nitrate/nitrite levels (multiparous: 2.5 ± 2 μmol/mg protein vs. virgins: 7 ± 1 μmol/mg protein) and endothelial nitric oxide synthase protein levels (multiparous: 0.53 ± 0.1 protein/actin vs. virgins: 1.0 ± 0.14 protein/actin). These data suggest that multiparity induces endothelial dysfunction through decreased NO bioavailability and increased reactive oxygen species formation.

scholarly journals Endothelial Dysfunction, Inflammation, and Oxidative Stress in COVID-19—Mechanisms and Therapeutic Targets

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Adriana Fodor ◽  
Brandusa Tiperciuc ◽  
Cezar Login ◽  
Olga H. Orasan ◽  
Andrada L. Lazar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Respiratory Failure ◽  
Endothelial Dysfunction ◽  
Clinical Manifestations ◽  
Therapeutic Targets ◽  
Lung Damage ◽  
Wide Range ◽  
Underlying Mechanisms ◽  
And Oxidative Stress

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.

scholarly journals Curcumin Mitigates Hypertension, Endothelial Dysfunction and Oxidative Stress in Rats with Chronic Exposure to Lead and Cadmium

2021 ◽  
Vol 253 (1) ◽  
pp. 69-76
Author(s):  
Akarachai Tubsakul ◽  
Weerapon Sangartit ◽  
Poungrat Pakdeechote ◽  
Veerapol Kukongviriyapan ◽  
Kwanjit Apaijit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Chronic Exposure ◽  
Lead And Cadmium ◽  
And Oxidative Stress

scholarly journals 60-Day Chronic Exposure to Low Concentrations of HgCl2 Impairs Sperm Quality: Hormonal Imbalance and Oxidative Stress as Potential Routes for Reproductive Dysfunction in Rats

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e111202 ◽  
Author(s):  
Caroline S. Martinez ◽  
João Guilherme D. Torres ◽  
Franck M. Peçanha ◽  
Janete A. Anselmo-Franci ◽  
Dalton V. Vassallo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Exposure ◽  
Sperm Quality ◽  
Reproductive Dysfunction ◽  
Low Concentrations ◽  
Hormonal Imbalance ◽  
And Oxidative Stress

scholarly journals Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis

2021 ◽  
Author(s):  
Arwa Fadıl Haqi BALLUR ◽  
Eyup ALTINOZ ◽  
Gurkan YİGİTTURK ◽  
Melike Ozgul Onal ◽  
Hulya ELBE ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gouty Arthritis ◽  
Total Antioxidant Status ◽  
Cellular Damage ◽  
Histopathological Changes ◽  
Markers Of Inflammation ◽  
Antioxidant Defense Systems ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Msu Crystals

Abstract Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and anti-oxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (On the 30th day, single dose 20 mg/ml, intraperitoneal), MSU+MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU+PINX and MSU+PINX+MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU+MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.

scholarly journals Indices of the DNA repair system in the brain of fish as a biomarker of inorganic mercury burden

2021 ◽  
Vol 32 (1) ◽  
pp. 9-16
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
R. O. Novitskyi ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Environmental Pollution ◽  
Dose Range ◽  
Inorganic Mercury ◽  
Mercury Chloride ◽  
Repair System ◽  
Fish Brain ◽  
Low Concentrations ◽  
The Brain

Mercury is a widespread heavy metal that causes a stable and prolonged environmental pollution. Low concentrations of inorganic and organic mercury compounds are found in almost all water bodies. The high level of mercury bioaccumulation is a cause of tissue-specific toxicity, including neurotoxicity. Absorbed in nervous tissue mercury can cause brain disorders both in neural and glial cells. The brain of fish is considered one of the most susceptible targets for cytotoxicity of mercury in aquatic ecosystems. Taking into account that different forms of mercury have widespread distribution and exhibit a strong neurotoxic effect, the assessment of mercury cytotoxicity in the brain of fish is relevant and extremely important. Rainbow trout Oncorhynchus mykiss was exposed to mercury chloride in the dose range of 5-20 μg/L for 60 days to study the chronic exposure of low doses. In this paper, we studied the influence of inorganic mercury on oxidative stress, DNA repair proteins – ERCC1 and PARP1 in the trout’s brain. The results obtained have shown that the chronic effect of inorganic mercury causes dose-dependent oxidative stress in the fish brain. In addition, low concentrations of mercury (10 and 20 μg/L) caused a decrease in the content of ERCC1 in the brain of fish. On the contrary, the same doses have caused an increase in PARP1 expression. That is the chronic influence of low concentrations of inorganic mercury has a negative effect in the fish brain. Observed results showed that inorganic mercury has a potential for suppressing DNA repair and, therefore, increases the instability of genome. Thus, ERCC1 and PARP1 can be considered as the sensitive biomarkers of mercury cytotoxicity in the fish brain. A further study of mercury neurotoxicity is needed to find out the hazard of mercury environmental pollution as well as a validation of biomarkers of their impact.

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