|
?:abstract
|
-
The eIF5A hypusination inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) was shown to protect from ischemic injuries. We hypothesized that GC7 could be useful for preconditioning kidneys from donors prior transplantation. Using a preclinical porcine brain-death (BD) donation model, we carried out in vivo evaluation of GC7 pre-treatment (3 mg/kg iv, 5 min after BD) at the beginning of the 4h-donor management, after which kidneys were collected, cold-stored (18h in UW) and one was allo-transplanted. Groups were defined as following (n=6 per group): healthy (CTL), untreated BD (Vehicle) and GC7-treated BD (Vehicule+GC7). At the end of 4h-management, GC7 treatment decreased BD-induced markers, as ROS markers. In addition, GC7 increased expression of mitochondrial-protective PGC1α and anti-oxidant proteins (SOD2, HO-1, NRF2 and Sirtuins). At the end of cold storage, GC7 treatment induced an increase of NRF2 and PGC1α mRNA and a better mitochondrial integrity/homeostasis with a decrease of DRP1-activation and increase of MFN2. Moreover, GC7 treatment significantly improved kidney outcome during 90 days follow-up after transplantation (fewer creatininemia and fibrosis). Overall, GC7 treatment was shown to be protective for kidneys against BD-induced injuries during donor management and subsequently appeared to preserve antioxidant defences and mitochondria homeostasis; these protective effects being accompanied by a better transplantation outcome.
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}