Fk506 Inhibit liver regeneration in HOC model Rat

by Selleckchem | Apr 30 2023

Background: Studies have shown that lymphocytes support hepatic oval cell (HOC)-dependent liver regeneration and FK506（Tacrolimus） is known as an immunosuppressor. Therefore, we studied the role of FK506 in HOC activation and/or proliferation to guide the clinical use of FK506.

Methods: Thirty male Lewis rats were randomly divided into 4 groups: (A) intervene in activation (n = 8), (B) intervene in proliferation (n = 8), (C) control HOC model (n = 8), and (D) pure partial hepatectomy (PH) (n = 6). The HOC model was established by 2AAF(2-acetylaminofluorene)/PH in groups A to C. FK506 (at a dose of 1 mg/kg/d) was given subcutaneously in group A except on operation day, and not until day 8 post-operation (PO) in group B. Half of the animals were euthanized on days 10 and 14 PO, respectively. The remnant liver was weighed and stained by hematoxylin and eosin and immunohistochemical staining of proliferating cell nuclear antigen and epithelial cell adhesion molecule enabled HOC proliferation analysis.

Results: FK506 intervention exacerbated liver damage and hindered the recovery of the HOC model rat. Weight gain was severely retarded or even negative. Liver weight and the liver body weight ratio were lower than control group. HE and immunohistochemistry showed pooer proliferation of hepatocytes and fewer HOC numbers in group A.

Conclusion: FK506 inhibited HOC activation by affecting T and NK cells, ultimately blocking liver regeneration. Poor liver regeneration after auxiliary liver transplantation might be associated with the inhibition of HOC activation and proliferation caused by FK506 treatment.

Comments：
The study aimed to investigate the effect of FK506 (Tacrolimus), an immunosuppressor, on hepatic oval cell (HOC)-dependent liver regeneration in rats. The HOC model was established using 2AAF/PH, and rats were divided into four groups, including an intervention group for activation and proliferation, a control group, and a pure partial hepatectomy group. FK506 was administered subcutaneously at a dose of 1mg/kg/d in the intervention group, except for the operation day and not until day 8 post-operation in the intervention group for proliferation. Half of the animals were euthanized on days 10 and 14 PO, respectively, and the remnant liver was analyzed for HOC proliferation.

The study's findings showed that FK506 intervention exacerbated liver damage and hindered the recovery of the HOC model rats. The weight gain was severely retarded or negative, and the liver weight and liver body weight ratio were lower than the control group. Histological analysis of the liver showed poor proliferation of hepatocytes and fewer HOC numbers in the intervention group for activation.

The study's conclusion indicated that FK506 inhibited HOC activation by affecting T and NK cells, ultimately blocking liver regeneration. The poor liver regeneration after auxiliary liver transplantation might be associated with the inhibition of HOC activation and proliferation caused by FK506 treatment.

In summary, the study highlights the importance of understanding the role of lymphocytes in supporting HOC-dependent liver regeneration and provides insights into the clinical use of FK506 in liver transplantation.