Preventive GC7 reduces brain death-induce renal injuries in a preclinical porcine model
S. Giraud
(1, 2, 3)
,
T. Kerforne
(1, 2, 4)
,
Philippine Couturier
(5, 2, 3)
,
S. Inal
(2, 3, 6)
,
P. Hannaert
(7, 1, 2)
,
M. Tauc
(8, 7)
,
T. Hauet
(5, 9, 2, 3, 6, 1)
1
Université de Poitiers - Faculté de Médecine et de Pharmacie
2 IRTOMIT [Poitiers] - Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques [U 1082]
3 Service de Biochimie
4 Département d’Anesthésie-Réanimation
5 GenESI - Génétique, Expérimentation et Système Innovants
6 FHU SUPORT - Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation
7 CNRS - Centre National de la Recherche Scientifique
8 LP2M - Laboratoire de PhysioMédecine Moléculaire
9 INRA - Institut National de la Recherche Agronomique
2 IRTOMIT [Poitiers] - Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques [U 1082]
3 Service de Biochimie
4 Département d’Anesthésie-Réanimation
5 GenESI - Génétique, Expérimentation et Système Innovants
6 FHU SUPORT - Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation
7 CNRS - Centre National de la Recherche Scientifique
8 LP2M - Laboratoire de PhysioMédecine Moléculaire
9 INRA - Institut National de la Recherche Agronomique
Résumé
N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A,
exhibits anti-inflammatory features and promotes anoxic/ischemic tolerance.
Thus, GC7 pretreatment could be useful in order to protect organs submitted to
ischemia before transplantation in heart-beating donors.
Methods: Using a pig brain death donation preclinical model, we carried out
the in vivo evaluation of GC7 pre-treatment (3 mg/kg iv bolus), after brain
death, at the beginning of the 4 h-reanimation, after which one kidney was
collected, cold-stored (18-h in UW), and allo-transplantated in a doublenephrectomized
recipient. Groups were defined as follows (n = 6 per group):
healthy (Control), untreated Brain death (BD) and GC7-treated BD (GC7).
Results: R1. At the end of 4 h-reanimation, GC7 decreased (80–100%,
p < 0.05) BD-increased markers: (i) eIF5A hypusination, (ii) tissue levels of
reactive oxygen species markers (CellRox staining and Aconitase), (iii) tissue
levels of nitrotyrosine, and (iv) the mitochondrial-dependent apoptosis pathway
(Bax/Bcl-2 proapoptotic ratio, Caspase-9). In addition, GC7 increased (2 to 6-
fold, p < 0.05) the expression of anti-oxidant proteins (SOD2 and HO-1, as well
as PGC-1a, Nrf2, and total & p-Sirtuin1 & 3). R2. At the end of cold storage,
GC7 treatment normalized BD-dependent decrease of SOD2 and HO-1
proteins expression (p < 0.05). In addition, GC7 significantly restored the BDdependent
increase of the Bax/Bcl-2 (proapoptotic) ratio (p < 0.05).
Conclusion: After the reanimation phase, preventively given GC7 proved
protective for kidneys against brain death-induced injuries; during the cold
storage phase, GC7 appeared to preserve antioxidant defences and to protect
mitochondria. Early and long-term, post-transplantation propagation of
observed protective effects are currently evaluated.
Domaines
Sciences du Vivant [q-bio]Format du dépôt | Fichier |
---|---|
Type de dépôt | Communication dans un congrès |
Titre |
en
Preventive GC7 reduces brain death-induce renal injuries in a preclinical porcine model
|
Résumé |
en
N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A,
exhibits anti-inflammatory features and promotes anoxic/ischemic tolerance.
Thus, GC7 pretreatment could be useful in order to protect organs submitted to
ischemia before transplantation in heart-beating donors.
Methods: Using a pig brain death donation preclinical model, we carried out
the in vivo evaluation of GC7 pre-treatment (3 mg/kg iv bolus), after brain
death, at the beginning of the 4 h-reanimation, after which one kidney was
collected, cold-stored (18-h in UW), and allo-transplantated in a doublenephrectomized
recipient. Groups were defined as follows (n = 6 per group):
healthy (Control), untreated Brain death (BD) and GC7-treated BD (GC7).
Results: R1. At the end of 4 h-reanimation, GC7 decreased (80–100%,
p < 0.05) BD-increased markers: (i) eIF5A hypusination, (ii) tissue levels of
reactive oxygen species markers (CellRox staining and Aconitase), (iii) tissue
levels of nitrotyrosine, and (iv) the mitochondrial-dependent apoptosis pathway
(Bax/Bcl-2 proapoptotic ratio, Caspase-9). In addition, GC7 increased (2 to 6-
fold, p < 0.05) the expression of anti-oxidant proteins (SOD2 and HO-1, as well
as PGC-1a, Nrf2, and total & p-Sirtuin1 & 3). R2. At the end of cold storage,
GC7 treatment normalized BD-dependent decrease of SOD2 and HO-1
proteins expression (p < 0.05). In addition, GC7 significantly restored the BDdependent
increase of the Bax/Bcl-2 (proapoptotic) ratio (p < 0.05).
Conclusion: After the reanimation phase, preventively given GC7 proved
protective for kidneys against brain death-induced injuries; during the cold
storage phase, GC7 appeared to preserve antioxidant defences and to protect
mitochondria. Early and long-term, post-transplantation propagation of
observed protective effects are currently evaluated.
|
Auteur(s) |
S. Giraud
1, 2, 3
, T. Kerforne
1, 2, 4
, Philippine Couturier
5, 2, 3
, S. Inal
2, 3, 6
, P. Hannaert
7, 1, 2
, M. Tauc
8, 7
, T. Hauet
5, 9, 2, 3, 6, 1
1
Université de Poitiers - Faculté de Médecine et de Pharmacie
( 108271 )
- Bâtiment D1 - 6, rue de la Milétrie - TSA 51115 - 86073 Poitiers Cedex 9
- France
2
IRTOMIT [Poitiers] -
Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques [U 1082]
( 182187 )
- Facultés de Médecine et Pharmacie - Campus CHU Poitiers - CS 90577. 2 rue de la Milétrie. 86021 Poitiers Cedex
- France
3
Service de Biochimie
( 180362 )
- Nantes, 44093
- France
4
Département d’Anesthésie-Réanimation
( 513295 )
- France
5
GenESI -
Génétique, Expérimentation et Système Innovants
( 508803 )
- INRA Magneraud - CS 40052 - 17700 SURGERES
- France
6
FHU SUPORT -
Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation
( 444102 )
- France
7
CNRS -
Centre National de la Recherche Scientifique
( 441569 )
- France
8
LP2M -
Laboratoire de PhysioMédecine Moléculaire
( 201743 )
- Parc Valrose 06108 Nice Cedex 2
- France
9
INRA -
Institut National de la Recherche Agronomique
( 92114 )
- France
|
ISSN |
0934-0874
|
Nombre de pages |
9-9
|
Public visé |
Scientifique
|
Sous-type de document pour les Communications |
Abstract
|
N° de brevet |
O18
|
Lieu de publication |
Hoboken (united kingdom)
|
Licence |
Paternité - Partage selon les Conditions Initiales
|
Langue du document |
Anglais
|
Source |
Abstracts of the 16th Annual Congress of the French Speaking Society of Transplantation
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Invité |
Non
|
Audience |
Non spécifiée
|
Actes |
Oui
|
Date de publication |
2017
|
Titre de la collection |
Transplant International
|
Volume |
30
|
Numéro |
Issue Supplement S1
|
Page/Identifiant |
29 p.
|
Titre du congrès |
16. Annual Congress of the French Speaking Society of Transplantation
|
Date début congrès |
2016-12-06
|
Date fin congrès |
2016-12-09
|
Ville |
Liège, Belgium
|
Pays |
Belgique
|
Domaine(s) |
|
Éditeur commercial |
|
DOI | 10.1111/tri.12885 |
ProdINRA | 388564 |
UT key WOS | 000390692000019 |
Origine :
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