Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress.
Animals
Apoptosis
/ drug effects
Cattle
Endothelial Cells
/ metabolism
Erectile Dysfunction
/ physiopathology
Hydrogen Peroxide
/ metabolism
Male
NADPH Oxidases
/ metabolism
Nitric Oxide
/ metabolism
Oxidative Stress
/ drug effects
Penile Erection
/ drug effects
Reactive Oxygen Species
/ metabolism
Sildenafil Citrate
/ pharmacology
Endothelial Damage
Erectile Dysfunction
Oxidative Stress
Radiation
Reactive Oxygen Species
Journal
The journal of sexual medicine
ISSN: 1743-6109
Titre abrégé: J Sex Med
Pays: Netherlands
ID NLM: 101230693
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
07
01
2019
revised:
11
08
2019
accepted:
18
08
2019
pubmed:
6
10
2019
medline:
7
7
2020
entrez:
6
10
2019
Statut:
ppublish
Résumé
The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic. To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial cells. Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 μM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10-15 Gy. Generation of reactive oxygen species (ROS) was studied. Extracellular hydrogen peroxide (H Single high-dose radiation therapy induced NADPH oxidases (NOXs) activation and ROS generation via the proapoptotic ASMase/ceramide pathway. The radio-protective effect of sildenafil on BAECs was due to inhibition of this pathway. Here, we demonstrate for the first time that radiation activated NOXs and induced generation of ROS in BAECs. In addition, we showed that sildenafil significantly reduced radiation-induced O This is the first study demonstrating that single high-dose radiation therapy induced NOXs activation, resulting in the generation of O This study demonstrated that sildenafil protects BAECs from radiation-induced oxidative stress by reducing NOX-induced ROS generation, thus resulting in decreased endothelial dysfunction. Therefore, it provides a potential mechanism to better understand the atherogenic etiology of postradiation ED. Wortel RC, Mizrachi A, Li H, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med 2019;16:1721-1733.
Identifiants
pubmed: 31585804
pii: S1743-6095(19)31384-0
doi: 10.1016/j.jsxm.2019.08.015
pmc: PMC7269093
mid: NIHMS1590121
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
Nitric Oxide
31C4KY9ESH
Hydrogen Peroxide
BBX060AN9V
Sildenafil Citrate
BW9B0ZE037
NADPH Oxidases
EC 1.6.3.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1721-1733Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIGMS NIH HHS
ID : R15 GM114792
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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