DNA Damage and Augmented Oxidative Stress in Bone Marrow Mononuclear Cells from Angiotensin-Dependent Hypertensive Mice

Campagnaro, Bianca Prandi; Tonini, Clarissa Loureiro; Nogueira, Breno Valentim; Casarini, Dulce Elena; Vasquez, Elisardo C.; Meyrelles, Silvana S.

doi:10.1155/2013/305202

Cited by 17 publications

(24 citation statements)

References 78 publications

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“…Despite the impact of arterial hypertension on ROS production in BM cells is poorly understood in murine models, our data support the idea that 2K1C hypertension contributes to oxidative stress in BM cells, leading to unfavorable processes, such as DNA damage (Schupp et al, 2007;Campagnaro et al, 2013) and apoptosis (Endtmann et al, 2011).…”

Section: K1c Hypertension Affects Bone Marrow Cellssupporting

confidence: 82%

“…Some authors, including us, have observed alterations in DNA caused by hypertension (Schupp et al, 2007;Fandos et al, 2009;Campagnaro et al, 2012Campagnaro et al, , 2013. In this work, the DNA content analysis showed that 2K1C hypertension induces DNA fragmentation in BM cells, suggesting that the disease leads to DNA changes compromising the functionality of the cells.…”

Section: Dna Contentsupporting

confidence: 49%

“…We used a mouse model of 2K1C angiotensin-dependent hypertension as previously described (Nogueira et al, 2007(Nogueira et al, , 2012Campagnaro et al, 2013). Briefly, the animal was anesthetized (ketamine/xylazine 91/9.1 mg/kg, i.p.)…”

Section: Induction Of 2k1c Renovascular Hypertensionmentioning

confidence: 99%

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Renovascular Hypertension Leads to DNA Damage and Apoptosis in Bone Marrow Cells

Campagnaro

Tonini

Doche

et al. 2013

DNA and Cell Biology

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Angiotensin II (Ang II), which plays a pivotal role in the pathophysiology of the two-kidney, one-clip (2K1C) Goldblatt hypertension, has been associated with augmented generation of reactive oxygen species (ROS) in some cells and tissues. In the present study, we evaluated the influence of 2K1C hypertension on oxidative stress, DNA fragmentation, and apoptosis of bone marrow (BM) cells. Two weeks after the renal artery clipping or Sham operation, flow cytometry analysis showed a higher production of superoxide anions (approximately sixfold) and hydrogen peroxide (approximately twofold) in 2K1C hypertensive than in Sham normotensive mice. 2K1C mice also showed an augmented DNA fragmentation (54%) and apoptotic cells (21%). Our data show that the 2K1C renovascular hypertension is characterized by an increased production of ROS, DNA damage, and apoptosis of BM, which is a fundamental source of the cells involved in tissue repair.

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Section: K1c Hypertension Affects Bone Marrow Cellssupporting

confidence: 82%

Section: Dna Contentsupporting

confidence: 49%

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Renovascular Hypertension Leads to DNA Damage and Apoptosis in Bone Marrow Cells

Campagnaro

Tonini

Doche

et al. 2013

DNA and Cell Biology

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“…Elevated levels of ROS, which is a characteristic of a state of oxidative stress, has been reported in clinical and pre-clinical studies in many cardiovascular diseases, including diabetes, hypertension and atherosclerosis [3,11,24,34,35]. Although under physiological conditions ROS are continuously produced in most cells, the imbalance between ROS production and its degradation, can lead to genomic instability and, consequently, permanent changes in the genetic material, contributing to unfavourable processes, e.g.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil ameliorates biomarkers of genotoxicity in an experimental model of spontaneous atherosclerosis

et al. 2013

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BackgroundIt is well known that enhanced production of reactive oxygen species (ROS) leads to oxidative stress observed in atherosclerosis and that ROS can also cause damage in cellular macromolecules, including DNA. Considering previous report that sildenafil, an inhibitor of phosphodiesterase 5 (PDE5), has antioxidant effects, in the present study we evaluated the effect of this drug on genotoxicity of blood mononuclear cells (MNC) and liver cells from atherosclerotic apolipoprotein E knockout mice (apoE-/-).MethodsROS production in MNC was evaluated by flow cytometry with the fluorescent dye dihydroethidium (DHE), a method that has been used to quantify the production of superoxide anion, and DNA damage was evaluated in both MNC and liver cells using the alkaline comet assay. Sildenafil-administered apoE-/- mice were compared with strain-matched mice administered with vehicle and with C57BL/6 wild-type (WT) mice.ResultsMNC from apoE-/- vehicle exhibited a 2-fold increase in production of superoxide anion in comparison with WT. In contrast, sildenafil-administered apoE-/- mice showed superoxide anion levels similar to those observed in WT mice. Similarly, MNC and liver cells from apoE-/- vehicle mice showed a 4-fold and 2-fold augmented DNA fragmentation compared with WT, respectively, and sildenafil-administered apoE-/- mice exhibited minimal DNA damage in those cells similar to WT mice.ConclusionsApoE-/- mice chronically administered with sildenafil exhibited reduced levels of superoxide anion in MNC and less DNA fragmentation in MNC and liver cells, which are biomarkers of genotoxicity. Therefore, sildenafil may offer a new perspective to the use of PDE5 inhibitors to protect against DNA damage, in cells involved in the inflammatory and dyslipidemic processes that accompany atherosclerosis.

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“…This increased ratio is an indicator of enhanced cell survival [34]. Bone marrow is the major reservoir for adult organ-specific stem cells, including endothelial progenitor cells, hematopoietic stem cells, and mesenchymal stem cells [35]. Consequently, it is reasonable to propose that BM mesenchymal stem cells may be locally activated in livers of the irradiated rats and compensated the damaged cells.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic genes expression in γ-irradiated rats treated with wheat germ oil, zinc and /or bone marrow

Mohamed

Ahmed

2014

IJBAS

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Background: Liver inflammation or injury is a hallmark of ionizing radiation. Natural radio-protectors are found in plant materials such as wheat germ oil, in addition to other dietary antioxidants, such as zinc. Objectives: The present study was designed to evaluate the amelioration of mRNA levels of Bax, bcl-2, p53 and caspase-3 in the liver of γ-irradiated rats treated with wheat germ oil, zinc sulphate and/or bone marrow. Methods: Animals were exposed to an acute single dose of 5Gy whole body irradiation of gamma radiation from Gamma-cell 40 (cesium-137) source. RNA was extracted from hepatic tissue homogenate and reverse transcribed into cDNA using RT-PCR kit. Results: A significant elevation was observed in hepatic level of mRNA of Bax and caspase 3, while levels of bcl-2 and p53 mRNA were decreased in irradiated rats as compared to control. A combination of bone marrow and wheat germ oil caused a significant reductions in hepatic mRNA levels of Bax and caspase 3 (3.1 and 1.5-fold, respectively), associated with a significant comparable elevation in hepatic mRNA level of p53 (2.7-fold), compared to the irradiated group. Conclusions: Results obtained from this study suggest that supplementation of wheat germ oil with either BM or zinc to irradiated rats down regulates the proapoptotic genes.

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DNA Damage and Augmented Oxidative Stress in Bone Marrow Mononuclear Cells from Angiotensin-Dependent Hypertensive Mice

Cited by 17 publications

References 78 publications

Renovascular Hypertension Leads to DNA Damage and Apoptosis in Bone Marrow Cells

Renovascular Hypertension Leads to DNA Damage and Apoptosis in Bone Marrow Cells

Sildenafil ameliorates biomarkers of genotoxicity in an experimental model of spontaneous atherosclerosis

Apoptotic genes expression in γ-irradiated rats treated with wheat germ oil, zinc and /or bone marrow

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