Uncoupling protein-2 induction in rat hepatocytes after acute carbon tetrachloride liver injury

This study is focused on the role of UCP-2 in hepatic oxidative metabolism following acute CCl₄ administration to rats. UCP-2 mRNA, almost undetectable in the liver of controls, was significantly increased 24 h after CCl₄ administration, peaked at 72 h and then tended to disappear. UCP-2 protein, undetectable in controls, increased 48-72 h after CCl₄ treatment. Experiments with isolated liver cells indicated that in control rats UCP-2 was expressed in non-parenchymal cells and not in hepatocytes, whereas in CCl₄-treated rats UCP-2 expression was induced in hepatocytes and was not affected in non-parenchymal cells. Addition of CCl₄ to the culture medium of hepatocytes from control rats failed to induce UCP-2 expression. Liver mitochondria from CCl₄-treated rats showed an increase of H₂O₂ release at 12-24 h, followed by a rise of TBARS. Vitamin E protected liver from CCl₄ injury and reduced the expression of UCP-2. Treatment with GdCl₃ prior to CCl₄, in order to inhibit Kupffer cells, reduced TBARS and UCP-2 mRNA increase in hepatic mitochondria. Our data indicate that CCl₄ induces the expression of UCP-2 in hepatocytes with a redox-dependent mechanism involving Kupffer cells. A role of UCP-2 in moderating CCl₄-induced oxidative stress during tissue regeneration after injury is suggested.