ArticleLipids in health and disease2013
Sildenafil ameliorates biomarkers of genotoxicity in an experimental model of spontaneous atherosclerosis.
Article in Lipids in health and disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 26 citations in OpenAlex.
- The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2020Article
- Worsening of Oxidative Stress, DNA Damage, and Atherosclerotic Lesions in Aged LDLrOxidative medicine and cellular longevity · 2019Article
- Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis.Biological research · 2018Article
- Solanum trilobatum L. Ameliorate Thioacetamide-Induced Oxidative Stress and Hepatic Damage in Albino Rats.Antioxidants (Basel, Switzerland) · 2017Article
- Protective effect of sildenafil on the genotoxicity and cytotoxicity in apolipoprotein E-deficient mice bone marrow cells.Lipids in health and disease · 2016Article
- Inhibition of PDE5 Restores Depressed Baroreflex Sensitivity in Renovascular Hypertensive Rats.Frontiers in physiology · 2016Article
- Effects of tobacco smoking during pregnancy on oxidative stress in the umbilical cord and mononuclear blood cells of neonates.Journal of biomedical science · 2014Article
- Renoprotective, anti-oxidative and anti-apoptotic effects of oral low-dose quercetin in the C57BL/6J model of diabetic nephropathy.Lipids in health and disease · 2014Article
- Inhibition of phosphodiesterase 5 restores endothelial function in renovascular hypertension.Journal of translational medicine · 2014Article
- Sildenafil ameliorates oxidative stress and DNA damage in the stenotic kidneys in mice with renovascular hypertension.Journal of translational medicine · 2014Article
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6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
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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