Abstract

Recently, we reported that 3,3′,5-triiodothyronine (T 3) induces the expression of redox-sensitive genes as a nongenomic mechanism of T 3 action. In this study, we show that T 3 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 β-fibrinogen is significantly augmented, a change that is suppressed by pretreatment with α-tocopherol (100 mg/kg ip) or gadolinium chloride (10 mg/kg iv) before T 3. It is concluded that T 3 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. © 2006 Elsevier Inc. All rights reserved.