[en] Background:
Whole-body irradiation induces renal ischemic preconditioning (RIP) in mice, possibly via neoangiogenesis.
Here, we test whether Sunitinib-mediated inhibition of angiogenesis prevents the irradiation-associated
RIP.
● Methods:
After kidney-centred irradiation (8.56 Gy), the right kidneys were removed and harvested, and the left
kidneys underwent ischemia (30min) / reperfusion (48h) (I/R) at Day 14. Three groups were compared
(n=8/group): 1/irradiation; 2/irradiation and gavage with Sunitinib (40 mg/kg) from D2 to D13; 3/control
group without irradiation or gavage. Renal sections from the 3 groups post-I/R were stained by Periodic
Acid Schiff (PAS). I/R-associated acute tubular necrosis was blindly evaluated by a renal pathologist using
the histological Jablonski score. The expression of inflammatory markers CD11b and F4/80 was
comparatively quantified by immunostaining. The expression of vascular markers CD31 and VEGF in nonischemic kidneys were quantified by real-time qPCR.
● Results:
One-way analysis of variance followed by Tukey’s test showed that, following I/R, serum levels of urea
(BUN) and creatinine (SCr) were significantly lower in pre-irradiated mice compared to controls (BUN:
106.1±33.6 vs. 352.2±54.3mg/dl; SCr: 0.3±0.13 vs. 1±0.2mg/dl), as well as in pre-irradiated mice compared
to the irradiated mice fed with Sunitinib (BUN: 106.1±33.6 vs. 408.4±54.9mg/dl; SCr: 0.3±0.12 vs.
1.5±0.3mg/dl). No difference was observed between the Sunitinib group and the control group. Jablonski’s
severity score was lower in pre-irradiated mice compared to control group and Sunitinib group (p<0.01).
The renal infiltration by CD11b- (560±32 vs. 308±21/mm²) and F4-80 positive cells (430±35 vs.
312±19/mm²) was significantly reduced in the irradiated group compared to controls. At mRNA levels, the
renal expression of VEGF and CD31 was increased in the irradiated group but not in the Sunitinib group
(p<0.01).
● Conclusions:
Renal irradiation before I/R is associated with preserved renal function and attenuated inflammation post
I/R. Sunitinib administration prevents the irradiation-induced RIP.
Research center :
GIGA‐R - Giga‐Research - ULiège
Disciplines :
Urology & nephrology
Author, co-author :
Khbouz, Badr ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
LALLEMAND, François ; Centre Hospitalier Universitaire de Liège - CHU > Département de Physique Médicale > Service médical de radiothérapie
