Poster (Scientific congresses and symposiums)The irradiation-induced renal ischemic preconditioning is blunted by the oral administration of the anti-angiogenic agent, Sunitinib
Khbouz, Badr; LALLEMAND, François; Rowart, Pascal et al.
2021 • Annual meeting Belgian Society of Nephrology 2021
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Abstract :
[en] ● Objective:
Irradiation has been suggested to induce renal ischemic preconditioning (RIP) in mice, possibly via angiogenesis. First, we comprehensively investigate the pathways involved in kidneys-centered irradiation. Next, we assess the functional impact of renal irradiation applied before renal ischemia/reperfusion (I/R) injury. Finally, we test whether Sunitinib-mediated inhibition of the angiogenesis prevents irradiation-associated RIP.
● Methods:
Exp1: Renal irradiation (8.56 Gy) was performed in male C57bl/6 mice (n=10). One month later, total kidney RNA was extracted from irradiated and control (n=5) mice for comparative RNA-Seq.
Exp2: After renal irradiation, the right kidneys were removed, and the left kidneys undergo ischemia(30min)/reperfusion(48h) at Days 7-14-28 post irradiation (n=8).
Exp3: Following the same protocol of I/R at Day14, 3 groups were compared (n=8): 1/irradiation; 2/irradiation and gavage with Sunitinib from Day2 to 13; 3/control group without irradiation or gavage.
● Results:
Exp1: RNA-Seq showed up-regulation of angiogenesis signaling pathways. Expressions of angiogenesis markers (CD31, VEGF) showed an increase at both mRNA and protein levels in irradiated kidneys (p<0.01).
Exp2: Following I/R, BUN and SCr levels were lower in the irradiated mice compared to controls: (BUN: 86.2±6.8 vs. 454.5±27.2mg/dl; SCr: 0.1±0.01 vs. 1.7±0.2mg/dl, p<0.01). The renal infiltration by CD11b (187±32 vs. 477±20/mm²) and F4-80 positive cells (110±22 vs.212±25/mm²) was reduced in the irradiated group. VEGF and CD31, were increased in irradiated kidneys at both mRNA and protein levels (p<0,01).
Exp3: One-way analysis of variance followed by Tukey’s test showed that, following I/R, BUN and SCr levels were lower in irradiated group compared to controls (BUN: 106.1±33.6 vs. 352.2±54.3mg/dl; SCr: 0.3±0.13 vs. 1±0.2mg/dl), and in irradiated group compared to the irradiated-exposed group to Sunitinib (BUN: 106.1±33.6 vs. 408.4±54.9mg/dl; SCr: 0.3±0.12 vs. 1.5±0.3mg/dl; p<0.01).
● Conclusions:
Kidneys-centered irradiation induces the activation of angiogenesis pathways in mice. Renal irradiation leads to RIP, with preserved renal function and attenuated inflammation post I/R. Exposure to the anti-angiogenic drug Sunitinib post-irradiation prevents the irradiation-induced RIP.
