Abstract
This study is focused on the role of UCP‐2 in hepatic oxidative metabolism following acute CCl~4~ administration to rats. UCP‐2 mRNA, almost undetectable in the liver of controls, was significantly increased 24 h after CCl~4~ administration, peaked at 72 h and then tended to disappear. UCP‐2 protein, undetectable in controls, increased 48–72 h after CCl~4~ 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 CCl~4~‐treated rats UCP‐2 expression was induced in hepatocytes and was not affected in non‐parenchymal cells. Addition of CCl~4~ to the culture medium of hepatocytes from control rats failed to induce UCP‐2 expression. Liver mitochondria from CCl~4~‐treated rats showed an increase of H~2~O~2~ release at 12–24 h, followed by a rise of TBARS. Vitamin E protected liver from CCl~4~ injury and reduced the expression of UCP‐2. Treatment with GdCl~3~ prior to CCl~4~, in order to inhibit Kupffer cells, reduced TBARS and UCP‐2 mRNA increase in hepatic mitochondria. Our data indicate that CCl~4~ induces the expression of UCP‐2 in hepatocytes with a redox‐dependent mechanism involving Kupffer cells. A role of UCP‐2 in moderating CCl~4~‐induced oxidative stress during tissue regeneration after injury is suggested. J. Cell. Physiol. 216: 413–418, 2008. © 2008 Wiley‐Liss, Inc.