Liver pathology and cell proliferation after calcineurin ınhibitors and antiproliferative drugs following partial hepatectomy in rats

Abstract

Immunosuppressants are the cornerstones of treatment after solid organ transplantation. This study investigated the pathology and cell proliferation following partial hepatectomy (PH) in rats undergoing immunosuppressive treatment. After 1 day, all rats were subjected to 70% PH. Groups A and B (n 10) received calcineurin inhibitors subcutaneously: either FK506 or cyclosporine (CyA). Groups C and D (n 10) received antiproliferative drugs: either mycophenolate mofetil (MMF) or sirolimus (SRL) by gavage. A control group (n 5) received 1 mL of tap water daily. On postoperative day 2, all rats were sacrificed to obtain liver tissue for pathologic examination. Using immunohistochemistry we separately examined the hepatectomy surface and the liver parenchyma. In the parenchyma, the Ki-67 indices were higher in the CyA and FK506 groups and lower in the SRL and MMF groups compared with controls (P .01). CyA had the highest and MMF the lowest values. On the hepatectomy surface, Ki-67 indices and TGF-alpha expressions were higher in the CyA group and lower in the SRL and MMF groups compared with the control group (P .01). Slightly higher values in the FK506 group were not significantly different compared with the control group (P .05). All groups other than FK506 showed prominent cholangiolar epithelial phenotypes compared with the control group. In the CyA and SRL groups, the number of cholangiolar cells was higher (P .01), and in the MMF group lower than in the control group (P .01). Among all groups, SRL had the highest values.