Tapia Gladys, Fernández Virginia, Pino Cesar, Ardiles Rodrigo, Videla Luis A
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 7, Chile.
Free Radic Biol Med. 2006 May 1;40(9):1628-35. doi: 10.1016/j.freeradbiomed.2005.12.033. Epub 2006 Jan 25.
Recently, we reported that 3,3',5-triiodothyronine (T3) induces the expression of redox-sensitive genes as a nongenomic mechanism of T3 action. In this study, we show that T3 administration to rats (daily doses of 0.1 mg/kg ip for 3 consecutive days) induced a calorigenic response and liver glutathione depletion as an indication of oxidative stress, with higher levels of interleukin (IL)-6 in serum (ELISA) and hepatic STAT3 DNA binding (EMSA), which were maximal at 48-72 h after treatment. Under these conditions, the protein expression of the acute-phase proteins haptoglobin and beta-fibrinogen is significantly augmented, a change that is suppressed by pretreatment with alpha-tocopherol (100 mg/kg ip) or gadolinium chloride (10 mg/kg iv) before T3. It is concluded that T3 administration induces the acute-phase response in rat liver by a redox mechanism triggered at the Kupffer cell level, in association with IL-6 release and activation of the STAT3 cascade, a response that may contribute to reestablishing homeostasis in the liver and extrahepatic tissues exhibiting oxidative stress.
