대한신장학회

논문분류	춘계학술대회 초록집
제목	A Novel Mitochondria-targeted Antioxidant Compound Attenuates Ischemia Reperfusion Renal Injury
저자	Dae Eun Choi1, Jin Young Jeong1, Hyun Su Choi2, Yoon Kyung Chang2, Sarah Chung1, Ki Ryang Na1, Kang Wook Lee1
출판정보	2015; 2015(1):
키워드	미토콘드리아,허혈재관류,항산화물질
초록	Introduction: Recently mitochondrial damage has been known to major role in various renal injury 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, reduce mitochondrial reactive oxygen species and improve cell survival. We therefore used NecroX-7, one of these compounds, and assessed its effects on renal damage. Methods: in vitro, IR was simulated by mineral oil in HK-2 cells. Mitochondrial respiratory complex, membrane potential, and reactive oxygen generation were evaluated in control and IR HK-2 cell with or without NecroX-7. Cell survival also evaluated. In vivo 10 weeks C57BL/6 mice were divided into 4 groups; vehicle (n=5) and NecroX-7 (10mg/kg intraperitoneal injection) treated sham group (n=5), vehicle n=7)d NecroX-7(n=7) with IR (reperfusion 27 minutes after clamping of both renal artery and vein) renal injury. 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. Results: NecroX-7 treatment significantly increase survival of IR HK-2 cell. NecroX-7 treatment increase mitochondrial complex IV and oxygen consumption rate. Also it decrease the 3NT and 8-OH deoxyguanosine generation. in vivo, The levels of BUN and serum creatinine in IR renal injury with NecroX7 treated mice were significantly lower than that of vehicle with IR injured mice (p <0.05). In microscopy, NecroX7 significantly reduced renal tubular epithelial cell necrosis and detachment. NecroX7 significantly reduced 8-OH deoxyguanosine positive and TUNEL positive cells in IR kidney. Also it significantly decreased the level of Bax/Bcl-2 ratio and phosphorylated caspase -3. Conclusion: In conclusion, NecroX-7 enhance mitochondrial respiratory complex IV and reduce mitochondrial damage and ROS generation. Also it attenuates ischemia reperfusion renal injury.
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