MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys.
MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys.
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DOI：
10.1371/journal.pone.0048590
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Macmillan-Crow LA
中科院分区：
文献类型：
--
作者：
Parajuli N;Campbell LH;Marine A;Brockbank KG;Macmillan-Crow LA
冷保存极大地促进了身体肾脏移植的使用，但在保存过程中会发生损伤。众所周知，肾脏冷保存过程中氧化剂的产生增加，线粒体是损伤的关键靶点。我们的实验室已经证明，冷保存肾细胞和大鼠肾脏会导致线粒体超氧化物歧化水平增加和线粒体电子传递链损伤，而在保存液中添加Mitoquone(MitoQ)可以钝化这种损伤。为了更好地翻译动物研究，纳入大型动物模型对于开发安全的临床前方案是必要的。因此，我们采用标准供体模型验证了这样一种假设，即在冷藏溶液中添加MitoQ可以通过减少氧化应激来保护线粒体功能，从而减少冷保存猪肾脏过程中肾小管的损伤。结果表明，冷藏可显著诱导氧化应激(硝基酪氨酸)、肾小管损伤和细胞死亡。使用高分辨率呼吸测量仪和新鲜的猪肾活检组织来评估线粒体功能，我们发现MitoQ在冷藏24小时后显着改善了电子传递链的复合II/III呼吸。此外，MitoQ可减轻48小时后的氧化应激、肾小管损伤和细胞死亡。这些结果表明，MitoQ通过改善冷藏期间的线粒体功能，减少了氧化应激、肾小管损伤和细胞死亡。因此，该化合物应被认为是器官移植前保存液的组成部分。
Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation.
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DOI：
10.1124/jpet.110.176743
发表时间：
2011-03-01
影响因子：
3.5
作者：
Mitchell, Tanecia;Rotaru, Dumitru;MacMillan-Crow, Lee Ann
通讯作者：
MacMillan-Crow, Lee Ann
影响因子：
6.2
作者：
Moers, Cyril;Varnav, Oana C.;Ploeg, Rutger J.
通讯作者：
Ploeg, Rutger J.
影响因子：
7.4
作者：
Mukhopadhyay, Partha;Horvath, Bela;Zsengeller, Zsuzsanna;Zielonka, Jacek;Tanchian, Galin;Holovac, Eileen;Kechrid, Malek;Patel, Vivek;Stillman, Isaac E.;Parikh, Samir M.;Joseph, Joy;Kalyanaraman, Balaraman;Pacher, Pal
通讯作者：
Pacher, Pal
影响因子：
2.9
作者：
Muller, F;Crofts, AR;Kramer, DM
通讯作者：
Kramer, DM
影响因子：
--
作者：
Giraud S;Favreau F;Chatauret N;Thuillier R;Maiga S;Hauet T
通讯作者：
Hauet T