A Comparison of Ramipril and Bevacizumab to Mitigate Radiation-Induced Brain Necrosis: An Experimental Study.
Angiogenesis Inhibitors
/ therapeutic use
Angiotensin-Converting Enzyme Inhibitors
/ therapeutic use
Animals
Bevacizumab
/ therapeutic use
Brain
/ pathology
Frontal Lobe
/ pathology
Hypoxia-Inducible Factor 1, alpha Subunit
/ biosynthesis
Immunohistochemistry
Male
Necrosis
/ prevention & control
Platelet Endothelial Cell Adhesion Molecule-1
/ biosynthesis
Radiation Injuries, Experimental
/ pathology
Radiosurgery
/ adverse effects
Ramipril
/ therapeutic use
Rats
Rats, Wistar
Vascular Endothelial Growth Factor A
/ biosynthesis
Bevacizumab
CD31
HIF-1α
Radiation necrosis
Ramipril
VEGF
Journal
World neurosurgery
ISSN: 1878-8769
Titre abrégé: World Neurosurg
Pays: United States
ID NLM: 101528275
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
27
05
2020
revised:
10
08
2020
accepted:
12
08
2020
pubmed:
22
8
2020
medline:
18
5
2021
entrez:
22
8
2020
Statut:
ppublish
Résumé
Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is a new treatment approach for radionecrosis. In our study, we compared the prophylactic and therapeutic usage of a promising agent, ramipril (an angiotensin-converting enzyme inhibitor), with that of bevacizumab for reducing radiation-induced brain injury after high-dose stereotactic radiosurgery (SRS). A total of 60 Wistar rats were used. The rats were irradiated with a single dose of 50 Gy using a Leksell Gamma Knife device. Bevacizumab and ramipril were administered in the prophylactic protocol (starting the first day of SRS) and in the therapeutic protocol (starting the fourth week of SRS). Their usage was continued until 12 weeks, and the right frontal lobes of the rats were examined histologically (hematoxylin and eosin stain) and immunohistochemically (hypoxia-inducible factor [HIF]-1α, VEGF, and CD31 antibody expression). The expression of VEGF, HIF-1α, and CD31 had significantly increased at 12 weeks after SRS compared with the control group. The addition of bevacizumab or ramipril to SRS significantly mitigated the histological severity of radiation injury and the expression of VEGF, HIF-1α, and CD31. However, the prophylactic use of bevacizumab and ramipril seemed to be more effective than therapeutic administration. Our results also revealed that the greatest benefit was achieved with the use of prophylactic administration of bevacizumab compared with other treatment protocols. Ramipril might be a promising agent for patients with radionecrosis. Clinical studies are required to investigate the effective and safe doses of ramipril, which is an inexpensive, well-tolerated drug that can cross the blood-brain barrier.
Sections du résumé
BACKGROUND
Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is a new treatment approach for radionecrosis. In our study, we compared the prophylactic and therapeutic usage of a promising agent, ramipril (an angiotensin-converting enzyme inhibitor), with that of bevacizumab for reducing radiation-induced brain injury after high-dose stereotactic radiosurgery (SRS).
METHODS
A total of 60 Wistar rats were used. The rats were irradiated with a single dose of 50 Gy using a Leksell Gamma Knife device. Bevacizumab and ramipril were administered in the prophylactic protocol (starting the first day of SRS) and in the therapeutic protocol (starting the fourth week of SRS). Their usage was continued until 12 weeks, and the right frontal lobes of the rats were examined histologically (hematoxylin and eosin stain) and immunohistochemically (hypoxia-inducible factor [HIF]-1α, VEGF, and CD31 antibody expression).
RESULTS
The expression of VEGF, HIF-1α, and CD31 had significantly increased at 12 weeks after SRS compared with the control group. The addition of bevacizumab or ramipril to SRS significantly mitigated the histological severity of radiation injury and the expression of VEGF, HIF-1α, and CD31. However, the prophylactic use of bevacizumab and ramipril seemed to be more effective than therapeutic administration. Our results also revealed that the greatest benefit was achieved with the use of prophylactic administration of bevacizumab compared with other treatment protocols.
CONCLUSIONS
Ramipril might be a promising agent for patients with radionecrosis. Clinical studies are required to investigate the effective and safe doses of ramipril, which is an inexpensive, well-tolerated drug that can cross the blood-brain barrier.
Identifiants
pubmed: 32822951
pii: S1878-8750(20)31848-9
doi: 10.1016/j.wneu.2020.08.081
pii:
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Angiotensin-Converting Enzyme Inhibitors
0
Hif1a protein, rat
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Platelet Endothelial Cell Adhesion Molecule-1
0
Vascular Endothelial Growth Factor A
0
vascular endothelial growth factor A, rat
0
Bevacizumab
2S9ZZM9Q9V
Ramipril
L35JN3I7SJ
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e210-e220Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.