Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Introduction: Recently mitochondrial damage has been known to play a major role in various renal injury mechanisms including ischemia-reperfusion (IR) renal injury. Mitochondrial injury and reactive oxygen species (ROS) generation play a role in IR renal injury. NecroX-7 is recently developed compounds which are concentrated in mitochondria, and reduce mitochondrial reactive oxygen species and improve cell survival. We assessed the effects of NecroX-7 on IR renal injury.
Methods: Ischemic injury was induced by mineral oil on HK-2 cell culture, in vitro. Mitochondrial respiratory complex, membrane potential, and reactive oxygen generation were evaluated in control and ischemic HK-2 cells with or without NecroX-7. Cell survival was also evaluated. C57BL/6 mice (10 weeks old) were divided into 4 groups; vehicle (n=5) and NecroX-7 (10mg/kg intraperitoneal injection) treated sham groups (n=5), vehicle (n=7) and NecroX-7(n=7) treated IR (reperfusion 27 minutes after clamping of both renal arteries and veins) groups. Kidneys and blood were harvested 24hr after IR injury. We performed real time RT-PCR, western blot and immunohistochemistry for molecular study and H&E stain and PAS stain for histologic examination.
NecroX-7 treatment significantly increased survival of ischemic HK-2 cells. NecroX-7 treatment increased mitochondrial complex IV and oxygen consumption rate. Also it decreased the 3NT and 8-OH deoxyguanosine generation. The levels of BUN and serum creatinine in NecroX7 treated IR injured mice were significantly lower than those of vehicle treated IR injured mice (p <0.05). In microscopic examination, NecroX7 significantly reduced renal tubular epithelial cell necrosis and detachment. NecroX-7 reduced significantly 8-OH deoxyguanosine positive and TUNEL positive cells in IR injured kidneys. Also it significantly decreased the level of Bax/Bcl-2 ratio and phosphorylated caspase -3.
Conclusion: In conclusion, NecroX-7 enhances mitochondrial respiratory complex IV and reduces mitochondrial damage and ROS generation. Also it attenuates ischemia reperfusion renal injury.
CITATION INFORMATION: Lee K, Ham Y, Jeon J, Chang Y, Chung S, Na K, Choi D. NecroX-7 Attenuates Ischemia-Reperfusion Renal Injury. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Lee K, Ham Y, Jeon J, Chang Y, Chung S, Na K, Choi D. NecroX-7 Attenuates Ischemia-Reperfusion Renal Injury. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/necrox-7-attenuates-ischemia-reperfusion-renal-injury/. Accessed July 3, 2020.
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