EFFECT OF CYCLOSPORINE ON LIVER-REGENERATION AFTER ORTHOTOPIC REDUCED-SIZE HEPATIC TRANSPLANTATION IN THE RAT

These experiments were undertaken to study the effects of cyclosporine A (CsA) on liver regeneration after an isogeneic orthotopic reduced-s ize hepatic transplantation (RSHT) in rats. Male Wistar rats were trea ted with or without a daily injection of CsA beginning 24 hr before su rgery and were subjected to a 68% partial hepatectomy. A isogeneic ort hotopic reduced-size hepatic transplantation was performed in recipien t rats pretreated with or without CsA. A daily injection of CsA was co ntinued until the recipient rats were sacrificed. Animals were sacrifi ced at various time points (12, 24, 36, 48, and 72 hr) postoperatively . The incorporation of bromodeoxyuridine (BrdU) into the DNA of the re mnant hepatocytes was evaluated by immunohistochemical staining with a monoclonal antibody against BrdU. CsA (10 mg/kg/day) significantly au gmented BrdU incorporation into hepatocytes after hepatectomy. The max imum labeling index (LI) was observed at 24 hr after hepatectomy. In c ontrast, the maximum LI in the recipient rats not receiving CsA was se en at 36 hr after RSHT, and 10 mg/kg/day of CsA decreased the LI at 36 hr after RSHT. A lower dose of CsA (3 mg/kg/day), however, significan tly increased the LI in the recipient rats (P < 0.01), and it reached a peak at 24 hr after RSHT when compared to the transplant recipients not receiving CsA. The time course of the increase in the LI in the tr ansplant recipient rats receiving 3 mg/kg/day of CsA was similar to th at observed in the rats after hepatectomy. This dosage improved the de lay in the reduced-size hepatic transplant LI reaching its peak. These findings suggest that after RSHT the liver graft is more sensitive to both hepatotrophic and hepatotoxic effects of CsA.