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 (UCP₂), 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 UCP₂ in the regenerating liver 96 h after 68% partial hepatectomy (PH) on the self-protection of regenerating liver against carbon tetrachloride (CCl₄) poisoning. Hepatotoxicity was induced in vivo by administering CCl₄ to rats that had undergone PH. After CCl₄ 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 CCl₄ poisoning. UCP₂ expression was markedly elevated in the regenerating liver, and further increased after CCl₄ intoxication. Mitochondrial membrane potential and adenosine triphosphate stores maintained higher levels in the regenerating liver than in sham-operated liver after CCl₄ intoxication. The results showed that the regenerating liver exhibited a potent ability to resist CCl₄ intoxication, and the autoprotection of regenerating liver might result from reduction of ROS by UCP₂ and maintenance of higher ATP stores.