Kupffer-cell activity is essential for thyroid hormone rat liver preconditioning

We studied the role of Kupffer cell functioning in T-3 liver preconditioning against ischemia-reperfusion (IR) injury using the macrophage inactivator gadolinium chloride (GdCl3) previous to T-3 treatment. Male Sprague-Dawley rats given a single i.p. dose of 0.1 mgT(3)/kg were subjected to 1 h ischemia followed by 20 h reperfusion, in groups of animals pretreated with 10 mg GdCl3/kg iv. 72 h before T-3 or with the respective vehicles. IR resulted in significant enhancement of serum aspartate aminotransferase (3.3-fold increase) and tumor necrosis factor-alpha (93% increase) levels, development of liver damage, and diminished nuclear factor-kappa B DNA binding over control values. These changes, which were suppressed by the T-3 administration prior to IR, persisted in animals given GdCl3 before T-3 treatment, under conditions of complete elimination of ED2(+) Kupffer cells achieved in a time window of 72 h. It is concluded that Kupffer cell functioning is essential for T-3 liver preconditioning, assessed in a warm IR injury model by hepatic macrophage inactivation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.