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

Abstract

We studied the role of Kupffer cell functioning in T3 liver preconditioning against ischemia–reperfusion (IR) injury using the macrophage inactivator gadolinium chloride (GdCl3) previous to T3 treatment. Male Sprague–Dawley rats given a single i.p. dose of 0.1mgT3/kg were subjected to 1 h ischemia followed by 20 h reperfusion, in groups of animals pretreated with 10mgGdCl3/kg i.v. 72 h before T3 or with the respective vehicles. IR resulted in significant enhancement of serum aspartate aminotransferase (3.3-fold increase) and tumor necrosis factor- (93% increase) levels, development of liver damage, and diminished nuclear factor- B DNA binding over control values. These changes, which were suppressed by the T3 administration prior to IR, persisted in animals given GdCl3 before T3 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 T3 liver preconditioning, assessed in a warm IR injury model by hepatic macrophage inactivation.