Protective effects of combined ischemic preconditioning and ascorbic acid on mitochondrial injury in hepatic ischemia/reperfusion

被引:35
作者
Lee., Woo-Yong [1 ]
Lee, Jun-Seok [1 ]
Lee, Sun-Mee [1 ]
机构
[1] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, Gyeonggi, South Korea
关键词
ischemic preconditioning; ascorbic acid; hepatic ischemia/reperfusion; oxidative stress; mitochondrial; permeability transition; energy metabolism;
D O I
10.1016/j.jss.2006.08.043
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. This study examined the in vivo effects of ischemic preconditioning (IPC), ascorbic acid (AA), or a combination (IPC + AA) on the level of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). Materials and methods. A rat liver was preconditioned with 10 min of ischemia followed by 10 min of reperfusion, and then subjected to 90 min of ischemia followed by 5 h of reperfusion. The rats were pretreated with AA (100 mg/kg, i.v.) 5 min before the sustained ischemia. Results. I/R increased the aminotransferase activity and level of mitochondrial lipid peroxidation, whereas it decreased the reduced glutathione:oxidized glutathione ratio. Either the IPC or AA pretreatment alone attenuated these changes, with the effect being enhanced by IPC + AA. The level of mitochondrial glutamate dehydrogenase, which is specifically located in the matrix, decreased after I/R but this was prevented by IPC + AA. Significant peroxide production was observed after 10 min of reperfusion after sustained ischemia. This change was attenuated by either IPC or AA alone and was further attenuated by IPC + AA. The mitochondria isolated after I/R were rapidly swollen, indicating an opening of the permeability transition pore. However, this was markedly reduced by IPC + AA. The hepatic ATP level was lower after I/R, which was restored by IPC alone and IPC + AA. Conclusions. Our findings suggest that IPC and AA synergistically reduce the level of mitochondrial damage during I/R as a result of decreased postischemic oxidant stress. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:45 / 52
页数:8
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