TY - JOUR
T1 - Fragility of the electron transport chain and superoxide generation in mitochondria of the liver graft after cold ischemia
AU - Ohkohchi, Nobuhiro
AU - Endoh, Tadao
AU - Oikawa, Kousei
AU - Seya, Kazuhiko
AU - Satomi, Susumu
PY - 1999/4/27
Y1 - 1999/4/27
N2 - Background. After cold ischemia, electrons transferred in the electron transport chain may leak out of the mitochondria in proportion to the deterioration of mitochondrial oxidative phosphorylation. This seems to be one major cause of the lipid peroxidation that occurs mainly in the hepatocytes at reperfusion in liver transplantation. To examine this hypothesis, we investigated superoxide generation and the amount of oxidative phosphorylation in the mitochondria isolated from rat livers after cold preservation. Methods. Rat liver was preserved in University of Wisconsin solution at 4°C for 24 hr. The mitochondrial fraction was prepared, and the amount of ATP synthesis and superoxide generation was investigated. Superoxide generation in the electron transport chain of submitochondrial particles was also measured by a chemiluminescence recorder. Results. The amount of ATP synthesis was significantly decreased after 12 hr of cold preservation. In the whole mitochondria, superoxide production in the presence of succinate was approximately 1/2000 to 1/3000 less than that observed in the submitochondrial particles at any determination point, and superoxide production was not affected by cold preservation. In the presence of antimycin A, superoxide production in the mitochondria after 18 hr of preservation increased significantly. Conclusion. These results indicate that the electron transfer in the complex III of the mitochondrial membrane becomes leaky after long periods of cold ischemia, but that leakage of superoxide anion did not increase, although the mitochondrial respiratory phosphorylation was deteriorated. We conclude that superoxide through the mitochondrial membrane cannot cause lipid peroxidation in hepatocytes at reperfusion even after a long period of cold ischemia.
AB - Background. After cold ischemia, electrons transferred in the electron transport chain may leak out of the mitochondria in proportion to the deterioration of mitochondrial oxidative phosphorylation. This seems to be one major cause of the lipid peroxidation that occurs mainly in the hepatocytes at reperfusion in liver transplantation. To examine this hypothesis, we investigated superoxide generation and the amount of oxidative phosphorylation in the mitochondria isolated from rat livers after cold preservation. Methods. Rat liver was preserved in University of Wisconsin solution at 4°C for 24 hr. The mitochondrial fraction was prepared, and the amount of ATP synthesis and superoxide generation was investigated. Superoxide generation in the electron transport chain of submitochondrial particles was also measured by a chemiluminescence recorder. Results. The amount of ATP synthesis was significantly decreased after 12 hr of cold preservation. In the whole mitochondria, superoxide production in the presence of succinate was approximately 1/2000 to 1/3000 less than that observed in the submitochondrial particles at any determination point, and superoxide production was not affected by cold preservation. In the presence of antimycin A, superoxide production in the mitochondria after 18 hr of preservation increased significantly. Conclusion. These results indicate that the electron transfer in the complex III of the mitochondrial membrane becomes leaky after long periods of cold ischemia, but that leakage of superoxide anion did not increase, although the mitochondrial respiratory phosphorylation was deteriorated. We conclude that superoxide through the mitochondrial membrane cannot cause lipid peroxidation in hepatocytes at reperfusion even after a long period of cold ischemia.
UR - http://www.scopus.com/inward/record.url?scp=0033609067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033609067&partnerID=8YFLogxK
U2 - 10.1097/00007890-199904270-00015
DO - 10.1097/00007890-199904270-00015
M3 - Article
C2 - 10232570
AN - SCOPUS:0033609067
VL - 67
SP - 1173
EP - 1177
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 8
ER -