Effect of the immunosuppressants on hepatocyte proliferation and apoptosis in a young animal model of liver regeneration: an immunohistochemical study using tissue microarrays.
Hepatocyte proliferation and apoptosis (programmed cell death) occur during the liver parenchyma regeneration and the liver size modeling is mainly controlled by hepatocyte apoptosis. The purpose of the present study was to verify the influence of immunosuppressant drugs on these phenomena by utilizing tissue microarray techniques. Thirty-six weaning rats (age 21-23 days, weight 30-50 g) were divided into six groups: control, sham, hepatectomy, hepatectomy plus solumedrol, hepatectomy plus CsA, and hepatectomy plus Tac. The animals were killed one day after hepatectomy, and the remnant livers were weighed and harvested for tissue microarray sections. Liver cell proliferation was evaluated by staining for PCNA and apoptosis was detected by the TUNEL method. It was verified that CsA promoted a decrease in the liver weight, Tac and CsA decreased the proliferation index of hepatocytes, and glucocorticoid had no significant effects. The apoptosis index was not altered by hepatectomy or immunosuppressants. Our data indicate that, in the growing rat, CsA and Tac have negative effects on hepatocyte proliferation and have no effect on the hepatocyte apoptosis.
Tannuri
Ana Cristina A
AC
Pediatric Surgery Division, University of São Paulo Medical School, São Paulo, Brazil.
Tannuri
Uenis
U
Wakamatsu
Alda
A
Mello
Evandro S
ES
Coelho
Maria Cecília M
MC
Dos Santos
Neide Aparecida S R
NA
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000254:growth & development; D008115:Liver Regeneration / Q000187:drug effects* / Q000276:immunology; D046228:Microarray Analysis; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology*; D014886:Weaning
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus