Liver regeneration after orthotopic reduced-size hepatic transplantation in the rat

These experiments were undertaken to study the effects of cyclosporine on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation in rats. The incorporation of bromodeoxyuridine into the DNA of the remnant hepatocytes was evaluated at various time points by immunohistochemical staining. Cyclosporine (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index was observed at 24 hr after hepatectomy. In contrast, the maximum labeling index in the recipient rats not receiving cyclosporine was seen at 36 hr after reduced-size hepatic transplantation, and 10 mg/kg/day of cyclosporine decreased the labeling index at 36 hr after grafting. A lower dose of cyclosporine (3 mg/kg/day), however, significantly increased the labeling index in the recipient rats, which reached a peak at 24 hr after grafting as compared with the transplant recipients not receiving cyclosporine. This dosage shortened the time it took for the reduced-size hepatic transplant labeling index to peak. These findings suggest that after reduced-size hepatic transplantation, the liver graft is more sensitive to both hepatotrophic and hepatotoxic effects of cyclosporine.