Effect of the immunosuppressants on hepatocyte cells proliferation and apoptosis during liver regeneration after hepatectomy - molecular studies.
The regeneration and remodeling of the transplanted liver is the result of hepatocyte proliferation and apoptosis (programmed cell death). The purpose of this study was to verify the influence of immunosuppressants on the expression levels of genes: IL-6 (regulator of hepatocyte proliferation), pro-apoptotic (Bak and Bax) and anti-apoptotic (Bcl-Xl and Bcl-2). 36 newborn suckling rats (age 5-7 days, weight 6-10 g) were divided into four groups: hepatectomy, hepatectomy plus methylprednisolone, hepatectomy plus CsA and hepatectomy plus Tac. The same experiments were performed in 24 weaning rats (age 21-23 days, weight 30-50 g). The animals were killed one day after the hepatectomy and the remnant livers were analyzed. The livers of all animals exhibited histological changes of liver regeneration. The immunosuppressants did not promote any alteration on IL-6 gene expression levels. Methylprednisolone and CsA increased the expression levels of Bak gene in newborn rats. However, methylprednisolone and Tac promoted increased expression levels of Bcl-2 in all groups. We hypothesize that these effects explain the efficacy of these drugs on the treatment of acute and chronic liver rejection as the expression of Bcl-2 in cholangiocytes is decreased as a consequence of bile duct lesions
Tannuri
Uenis
U
University of São Paulo Medical School, São Paulo, Brazil. uenist@usp.br
Tannuri
Ana C A
AC
Coelho
Maria C A
MC
Mello
Evandro S
ES
dos Santos
Aparecida S R
AS
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D008775:Methylprednisolone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D016572:Cyclosporine; D016559:Tacrolimus; D008775:Methylprednisolone