A new suppressive agent against interleukin-1beta and tumor necrosis factor-alpha enhances liver regeneration after partial hepatectomy in rats.

In the present study, the effect of FR167653, a novel suppressive agent against interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), on liver regeneration was investigated in rats after partial hepatectomy (PH). Doses of 1, 3 and 5 mg/kg per h FR167653 (FR-1, FR-3 and FR-5, respectively) were given intravenously 30 min before PH, while the control was given normal saline. Serum chemistries were serially monitored, and liver regeneration was evaluated by remnant liver weight ratio, proliferating cell nuclear antigen (PCNA) labeling index and mitotic index. Accumulation of IL-1beta and TNF-alpha messenger RNA (mRNA) in the remnant liver was also measured. In FR167653-treated groups, the releases of alanine transaminase (ALT) and aspartate transaminase (AST) were lower. The PCNA labeling index was enhanced by FR167653-administration in a dose-dependent manner, FR-3 and FR-5 groups showed significantly higher peak DNA synthesis than the control group at 24 h post-PH (P<0.01). The mitotic index was also enhanced by FR167653-administration in a dose-dependent manner. In FR-5 group, the remnant liver weight ratio was significantly higher than that in the control group (P<0.05). The accumulation of IL-1beta messenger RNA (mRNA) in the remnant liver was obviously suppressed in FR-3 and FR-5 groups, but the expression of TNF-alpha mRNA was not apparently reduced. In conclusion, FR167653 ameliorates liver injury and enhances liver regeneration after PH in rats.