scholarly journals MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

2015 ◽  
Vol 283 (2) ◽  
pp. 127-138 ◽  
Author(s):  
Maylla Ronacher Simões ◽  
Andrea Aguado ◽  
Jonaína Fiorim ◽  
Edna Aparecida Silveira ◽  
Bruna Fernandes Azevedo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lead Exposure ◽  
Vascular Reactivity ◽  
Mapk Pathway ◽  
Cyclooxygenase 2 ◽  
Pathway Activation ◽  
Chronic Lead Exposure

Lead exposure effect on angiotensin II renal vasoconstriction

2007 ◽  
Vol 26 (6) ◽  
pp. 499-507 ◽  
Author(s):  
Hilda Vargas Robles ◽  
Eunice Romo ◽  
Alicia Sanchez-Mendoza ◽  
Amelia Rios ◽  
Virgilia Soto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Lead Exposure ◽  
Vascular Reactivity ◽  
Pure Water ◽  
Control Group ◽  
Water Control ◽  
Exposure Effect ◽  
Stress Changes ◽  
Chronic Lead Exposure

Low levels of chronic lead exposure can produce hypertension and endothelial dysfunction, which could be associated with oxidative stress, changes in vascular tone and an imbalance of endothelial-derived vasoconstriction and vasodilator factors. The aim was to investigate the effect of chronic lead-exposure on angiotensin II-induced vasoconstriction in isolated perfused kidney and microvessels. Male Wistar rats (230—250 g) were treated for 12 weeks with lead acetate (100 ppm, Pbgroup) or pure water (control group). We evaluated the vascular reactivity in the kidneys and renal microvessels in the presence and absence of Nω-nitro-L-arginine methyl ester (L-NAME) in both groups. The nitrite concentration in renal perfusate was measured as an index of NO released, renal abundance of 3-nitrotyrosine was measured as well as endothelial NO synthase (eNOS) expression. Oxidative stress was measured by using the oxidative fluorescence dye dihydroethidium (DHE) to evaluate in situ production of superoxide and identified by confocal microscopy. Lead-exposure significantly increased blood pressure, eNOS protein expression, oxidative stress and vascular reactivity to angiotensin II. L-NAME potentiated vascular response to angiotensin II in control group but had no effect on the Pb-group. Nitrites released from the kidney of lead-group was lower compared to the control group while 3-nitrotyrosine was higher. This data suggest that lead-induced hypertension could be caused partially by an altered NOsystem. Human & Experimental Toxicology (2007) 26: 499—507

Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas

2014 ◽  
Vol 67 ◽  
pp. 366-376 ◽  
Author(s):  
Edna Aparecida Silveira ◽  
Fabiana Dayse Magalhães Siman ◽  
Thaís de Oliveira Faria ◽  
Marcos Vinícius Altoé Vescovi ◽  
Lorena Barros Furieri ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Lead Exposure ◽  
Vascular Reactivity ◽  
Low Dose ◽  
Systolic Arterial Pressure ◽  
Chronic Lead Exposure

The effect of chronic lead exposure on the course of schistosomiasis in hamsters and the protective effect of the antioxidant preparation ‘Antox’

2003 ◽  
Vol 22 (9) ◽  
pp. 481-490 ◽  
Author(s):  
Mona El-Gohary ◽  
Abd-Elaziz Yassin ◽  
Maisa A Shalabya
Keyword(s):  
Oxidative Stress ◽  
Lead Exposure ◽  
Blood Lead ◽  
Treated Group ◽  
Egg Load ◽  
Control Group ◽  
Oxidative Stress Parameters ◽  
Lead Levels ◽  
Chronic Lead Exposure ◽  
Stress Parameters

Eighty adult male hamsters were used in this study, 20 of them were divided equally into a noninfected, nontreated control group and chronic lead exposed groups, which were given lead acetate intraperitoneally, dissolved in distilled water, 2 mg/kg/day for seven weeks. Then, two experiments were carried out on the remaining animals. Each experiment included 30 animals and was divided equally into three groups. Experiment A was carried out on the following groups: Schistosoma mansoni infected group, S. mansoni infected and chronic lead exposed group and S. mansoni infected, chronic lead exposed and ‘Antox’ treated group. Experiment B was done following the same design except that infection was carried out using Schistosoma haematobium cercaria. Chronic lead exposure of Schistosoma infected groups showed significant reductions in worm burden, tissue egg load and ova excretion in stool, liver and intestine. Compared with the control group, there were insignificant increases in serum and hepatic glutathione and malondialdehyde levels and a significant increase in hepatic 8-oxodeoxy guanosine phosphate (8-Ox-Dg) levels in Schistosomainfected groups. However, there was a significant increase in hepatic and blood lead levels, oxidative stress parameters and in the hepatic 8-Ox-Dg level in Schistosoma infected and chronic lead exposed groups as compared with their corresponding Schistosoma only infected groups. This study revealed a significant reduction in oxidative stress parameters as well as in blood and hepatic lead levels and in hepatic 8-Ox-Dg levels after giving Antox to the Schistosoma infected and chronic lead exposed groups. However, Antox increased insignificantly all the parasitological parameters studied in the Schistosoma infected and chronic lead exposed groups.

Mycophenolate mofetil administration reduces renal inflammation, oxidative stress, and arterial pressure in rats with lead-induced hypertension

2007 ◽  
Vol 293 (2) ◽  
pp. F616-F623 ◽  
Author(s):  
Yanauri Bravo ◽  
Yasmir Quiroz ◽  
Atilio Ferrebuz ◽  
Nosratola D. Vaziri ◽  
Bernardo Rodríguez-Iturbe
Keyword(s):  
Oxidative Stress ◽  
Mycophenolate Mofetil ◽  
Lead Exposure ◽  
Low Dose ◽  
Immune Cell ◽  
Cell Damage ◽  
Experimental Models ◽  
Renal Inflammation ◽  
Induced Hypertension ◽  
Chronic Lead Exposure

Hypertension is a likely consequence of chronic lead exposure in humans, especially in association with reduced renal function and in high risk populations. Numerous studies have demonstrated that oxidative stress plays an important role in the pathogenesis of experimental lead-induced hypertension and we have shown recently that tubulointerstitial immune cell infiltration is a feature of chronic low-dose lead exposure. Since oxidative stress, renal inflammation, and angiotensin activity are closely linked characteristics in experimental models of hypertension, we decided to investigate whether lead-induced hypertension would be ameliorated by suppressing renal inflammation with the immunosuppressive drug mycophenolate mofetil (MMF). We studied rats exposed for 14 wk to lead acetate (100 ppm in the drinking water) that, in addition, received either MMF, 20 mg·kg−1·day−1 by gastric gavage (Pb.MMF group, n = 12) or vehicle (Pb group, n = 12). Control rats received MMF alone ( n = 5) or neither lead nor MMF ( n = 6). All rats were killed at the end of the experiment. Low-dose lead exposure resulted in mild to moderate tubular cell damage and a progressive increment in blood pressure, oxidative stress, interstitial accumulation of lymphocytes and macrophages, NF-κB activation, and increased renal angiotensin II level. The administration of MMF suppressed the tubulointerstitial accumulation of lymphocytes and macrophages and prevented the hypertension, oxidative stress, and NF-κB activation and reduced the heightened renal angiotensin content associated with chronic lead exposure. We conclude that interstitial inflammation plays an important role in lead-induced hypertension.

scholarly journals Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids

2021 ◽  
Vol 11 ◽  
Author(s):  
Maylla Ronacher Simões ◽  
Bruna Fernandes Azevedo ◽  
María Jesús Alonso ◽  
Mercedes Salaices ◽  
Dalton Valentim Vassallo
Keyword(s):  
Lead Exposure ◽  
Vascular Reactivity ◽  
Cyclooxygenase 2 ◽  
Resistance Arteries ◽  
Induced Hypertension ◽  
Pb Exposure ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Cox 2 Inhibitors

Lead (Pb) exposure causes hazardous effects as hypertension and other cardiovascular diseases. We evaluated whether chronic Pb exposure alters the peripheral vascular resistance measuring the vascular reactivity of mesenteric resistance arteries in rats to identify the underlying mechanisms that are associated to the development of Pb-induced hypertension. Mesenteric resistance arteries from lead-treated and untreated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) were used. Contractile responses to phenylephrine increased, while acetylcholine and sodium nitroprusside-induced relaxation was not affected by lead treatment. Endothelium removal and inhibition of NO synthase by L-NAME similarly enhanced the response to phenylephrine in untreated and lead-treated rats. The antioxidants apocynin and superoxide dismutase (SOD) did not affect vasoconstriction in either group. The vascular expression of cyclooxygenase-2 (COX-2) protein increased after lead exposure. The respective non-specific or specific COX-2 inhibitors indomethacin and NS398 reduced more strongly the response to phenylephrine in treated rats. Antagonists of EP1 (SC19220), TP (SQ29548), IP (CAY10441) and angiotensin II type 1 (losartan) receptors reduced vasoconstriction only in treated rats. These conclusions present further evidence that lead, even in small concentration, produces cardiovascular hazards being an environmental contaminant that account for lead-induced hypertension.

scholarly journals Estrogen Modulates Microglial Inflammatory Mediator Production via Interactions with Estrogen Receptor β

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5021-5032 ◽  
Author(s):  
Ann E. Baker ◽  
Vielska M. Brautigam ◽  
Jyoti J. Watters
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Cyclooxygenase 2 ◽  
No Production ◽  
Transcriptional Responses ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Microglial Cell Line ◽  
Antiinflammatory Effects

Abstract Estrogens are well known to exert antiinflammatory effects outside the central nervous system (CNS). They have also been shown to exert neuroprotective effects in the CNS after several types of injury, including neurodegeneration. However, the molecular mechanisms by which these effects occur remain unclear. Because microglial hyperactivation and their production of neurotoxins is associated with many types of brain injury for which estrogens are beneficial, we sought to investigate the ability of estrogen to modulate microglial function. Furthermore, because little is known regarding the role of each of the two known estrogen receptors (ERs) in microglia, our studies were designed to test the hypothesis that 17β-estradiol (E2) exerts antiinflammatory effects in microglia, specifically via interactions with ERβ. We tested this hypothesis using the murine microglial cell line BV-2, which naturally expresses only ERβ. Our results indicate that not only does E2 decrease lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, it also reduces the expression of cyclooxygenase-2, a target for estrogen that has not previously been reported for ERβ. We also observed that LPS-stimulated TNFα mRNA was increased by estrogen. E2 exerts these effects within 30 min compared with typical estrogen transcriptional responses. Tamoxifen and ICI 182,780 differentially blocked the inhibitory effects of E2 on LPS-stimulated iNOS and cyclooxygenase-2. In addition, we show that E2 alters LPS-stimulated MAPK pathway activation, supporting the idea that alterations in the MAPKs may be a potential mechanism by which ERβ mediates decreased microglial activation.

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