Recently, we demonstrated that 3,3′,5-triiodothyronine (T3) induces oxidative stress in rat liver, with enhancement in the DNA binding of nuclear factor-κB (NF-κB) and the NF-κB-dependent expression of tumor necrosis factor-α (TNF-α). 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-α (ELISA), liver inhibitor of κB (IκB-α) phosphorylation (Western blot analysis), and hepatic NF-κB 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 α-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-α release and activation of the IκB-α kinase/NF-κB cascade, which may constitute a protective mechanism against free radical toxicity involving cell death signaling.
In Vivo Transfection of Manganese Superoxide Dismutase Gene or Nuclear Factor κB shRNA in Nodose Ganglia Improves Aortic Baroreceptor Function in Heart Failure Rats
