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 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.