Recently, we demonstrated that 3,3',5-triiodothyronine (T3) induces oxidative stress in rat liver, with enhancement in the DNA binding of nuclear factor-kappaB (NF-kappaB) and the NF-kappaB-dependent expression of tumor necrosis factor-alpha (TNF-alpha). In this study, we show that T3 administration (daily doses of 0.1 mg/kg i.p. for three consecutive days) elicited a calorigenic response and higher liver O2 consumption rates, with increased serum levels of TNF-alpha (ELISA), liver inhibitor of kappaB (IkappaB-alpha) phosphorylation (Western blot analysis), and hepatic NF-kappaB DNA binding (EMSA) at 56-72 h after treatment. Within this time interval, liver manganese superoxide dismutase (MnSOD) activity and the protein expression of MnSOD and Bcl-2 are enhanced. These changes are abrogated by the administration of alpha-tocopherol (100 mg/kg i.p.) prior to T3. It is concluded that T3 treatment leads to the redox upregulation of MnSOD and Bcl-2 in rat liver, in association with TNF-alpha release and activation of the IkappaB-alpha kinase/NF-kappaB cascade, which may constitute a protective mechanism against free radical toxicity involving cell death signaling.