Evidence that ciclosporin is hepatotoxic and hepatotrophic in 70% hepatectomized rats and mice.

The influence of ciclosporin (Cs) on liver regeneration was studied in rats and mice with or without thymus after two-third hepatectomy. Rats were treated at -24, 0, and +24 h posthepatectomy with oral Cs, 5, 10, or 20 mg/kg. Before hepatectomy, mice were given a 4-day course of Cs 10 mg/kg. The peak mitosis (30 h posthepatectomy) of remnant hepatocytes in rats was doubled by the two lower dosages of Cs but was suppressed by the highest dosage compared with control. In addition, the rise in serum transaminase and total bilirubin concentrations was proportionate to the increase in Cs dosage given. Cs increased hepatocyte division in thymic mice but was hepatotoxic in athymic nude mice. These data present evidence that Cs is both hepatotrophic and hepatotoxic in regenerating liver.