Protection of regenerating liver after partial hepatectomy from carbon tetrachloride hepatotoxicity in rats: roles of mitochondrial uncoupling protein 2 and ATP stores.
Uncoupling protein 2 (UCP(2)), an inner mitochondrial membrane protein, can limit the generation of reactive oxygen species (ROS) and protect cells from injuries mediated by oxidative stress. We investigated the effect of upregulation of UCP(2) in the regenerating liver 96 h after 68% partial hepatectomy (PH) on the self-protection of regenerating liver against carbon tetrachloride (CCl(4)) poisoning. Hepatotoxicity was induced in vivo by administering CCl(4) to rats that had undergone PH. After CCl(4) poisoning, the regenerating liver appeared to have less histological damage and lower serum alanine aminotransferase (ALT) levels. Lower malondialdehyde production and higher glutathione contents were also observed in the regenerating liver compared with the sham-operated liver after CCl(4) poisoning. UCP(2) expression was markedly elevated in the regenerating liver, and further increased after CCl(4) intoxication. Mitochondrial membrane potential and adenosine triphosphate stores maintained higher levels in the regenerating liver than in sham-operated liver after CCl(4) intoxication. The results showed that the regenerating liver exhibited a potent ability to resist CCl(4) intoxication, and the autoprotection of regenerating liver might result from reduction of ROS by UCP(2) and maintenance of higher ATP stores.
Wu
Qiong
Q
Department of Physiology, Dalian Medical University, Dalian, Liaoning Province 116044, China.
Gong
Dezheng
D
Tian
Nan
N
Zhu
Liang
L
Guan
Lili
L
Yang
Mei
M
Yuan
Bo
B
Qiu
Quanfeng
Q
Lv
Huiming
H
Zou
Yuan
Y
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006498:Hepatectomy; D007473:Ion Channels / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D024101:Mitochondrial Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D002251:Carbon Tetrachloride; D005978:Glutathione