Inhibition by interferon α-2b of rat liver regeneration:: effect on ornithine decarboxylase and total protein synthesis

Polyamines are key factors in macromolecule synthesis during liver regeneration. It has been postulated that interferon-alpha (IFN alpha) decreases putrescine levels in regenerating liver by inhibiting ornithine decarboxylase (ODC) activity, the main enzyme in polyamine biosynthesis. In the present study, we analysed the effects of a pharmacological dose of IFN alpha on polyamine and ODC levels during the regenerative process following partial hepatectomy in rats. Synthesis of ODC by isolated hepatocytes from IFN-treated rats with regenerating livers was also assessed. Furthermore, we investigated the effect of IFN alpha -2b on DNA and total protein synthesis in 24-hr regenerating livers. No effect on DNA synthesis was observed at the dose of IFNa-2b used, but total protein synthesis decreased significantly in IFN alpha -2b-treated rats undergoing liver regeneration (7.0 +/- 2.0 and 12.1 +/- 1.7%.min(-1) in hepatectomized rats treated with IFN alpha -2b and saline, respectively). ODC levels were also reduced significantly (by 50%) in hepatectomized rats treated with IFN alpha -2b versus saline. In parallel with the ODC decrease, the concentrations of putrescine and spermidine (63 +/- 25 vs 101 +/- 15 nmol/g liver and 1.08 +/- 0.35 vs 2.14 +/- 0.22 mu mol/g liver, respectively, in IFN alpha -2b- and saline-treated hepatectomized rats) showed similar, significant diminutions. Moreover, the incorporation of [S-35]methionine into ODC was decreased dramatically in isolated hepatocytes from IFN alpha -2b-treated hepatectomized rats 12 hr after surgery. In conclusion, the protein synthesis rate in regenerating liver was impaired by therapeutic doses of IFN alpha -2b. In addition, the results presented in this study suggest that IFN alpha -2b negatively regulates ODC synthesis, causing a reduction in polyamine levels during liver regeneration. (C) 2001 Elsevier Science Inc. All rights reserved.