Effects of immunosuppressants on hepatocyte cell mitosis during liver regeneration in growing animal models of partial hepatectomy.
OBJECTIVE
We sought to evaluate the effects of immunosuppressant drugs (corticosteroid, cyclosporine [CsA], and tacrolimus [Tac]) on liver regeneration in growing animals submitted to 70% hepatectomy.


METHODS
Newborn and weaning rats were submitted to 70% hepatectomy receiving separately methylprednisolone, CsA, or Tac. All animals were sacrificed 24 hours after the procedure. The remnant liver lobes were subjected to histomorphometric analyses with determination of hepatocyte mitotic index.


RESULTS
Administration of immunosuppressants did not change the mitotic index of the regenerating liver in newborn animals. In weaning rats, methylprednisolone reduced the mitotic index (P = .01) and Tac caused a greater increase in this rate (P = .001). CsA had no effect on mitotic index. The number of hepatocyte mitoses in newborn animal livers was greater than that in weaning animal livers (P = .001).


CONCLUSIONS
In situations in which intense, fast processes of liver regeneration are crucial, the advantages of the use of Tac must be considered, such as in pediatric transplant patients.
Tannuri
A C A
AC
Pediatric Surgery Laboratory (LIM-30) and Liver Function Research Laboratory (LIM-14), University of São Paulo Medical School, São Paulo, Brazil.
Tannuri
U
U
Coelho
M C M
MC
Mello
E S
ES
Santos
N A S R
NA
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D016572:Cyclosporine / Q000494:pharmacology*; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008115:Liver Regeneration / Q000502:physiology*; D008775:Methylprednisolone / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D008940:Mitotic Index; D023421:Models, Animal; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology*; D014886:Weaning
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus; D008775:Methylprednisolone