Augmentative Effect of Cyclosporin A on Rat Liver Regeneration: Influence on Hepatocyte Growth Factor and Transforming Growth Factor-β1

Abstract

We investigated the effect of cyclosporin A (CsA) on rat liver regeneration following partial hepatectomy with reference to cytokine production. Rats were divided into two groups: those without CsA pretreatment (group 1) and those with CsA pretreatment (group 2). Animals were given olive oil vehicle or CsA (10 mg/kg) dissolved in olive oil daily by gavage from 4 to 1 days before hepatectomy. The ratio of regenerating liver weight to initial body weight in group 2 was significantly higher than that in group 1 at 72 h. Although a peak 5-bromo-2-deoxyuridine labeling index was found at 24 h after hepatectomy in both groups, the peak value in the CsA-treated animals was significantly higher than in controls. In both groups, hepatocyte growth factor concentrations in both plasma and liver tissue showed maximal values at 12 h. Liver tissue values in group 2, however, were significantly higher from 1 to 12 h compared to group 1. Transforming growth factor-β1 (TGF-β1) concentrations showed minimal serial changes in group 1, while those in liver tissue of group 2 rats were significantly lower than in group 1. Plasma TGF-β1 concentrations did not differ. These results suggest that upregulation of hepatic regeneration with CsA pretreatment might be attributed in part to changes in production of these mitogenic and mitoinhibitory cytokines.