Interleukin-1 (IL-1) and
tumor necrosis factor (TNF) are
cytokines commonly associated with inflammatory conditions such as hepatic injury after
ischemia-reperfusion.
FR167653 has been characterized as a potent suppressant of IL-1beta and
TNF-alpha production. In this study, we evaluated the effect of
FR167653 in an extended liver resection with
ischemia in a dog model. The right portal pedicle was clamped for 60 minutes, while the left portal branch was patent to avoid portal congestion. Following reperfusion, 75% of the liver (including the right central, quadrate, left central, left lateral, and papillary lobes) were resected. Animals were divided into two groups: a control group (n = 10), and a FR-treated group (n = 6) in which
FR167653 was administered via the portal vein. Hepatic venous blood was collected to measure
alanine transaminase (ALT),
aspartate transaminase (AST),
lactate dehydrogenase (LDH),
purine nucleoside phosphorylase (PNP), and
hyaluronic acid (HA) levels, and IL-1beta expression was also measured by
reverse-transcriptase polymerase chain reaction (RT-PCR). ALT, AST, LDH, PNP, and HA levels after reperfusion were significantly lower (P < .05) in the FR-treated group than in the control group, and the FR-treated group showed inhibited IL-1beta expression. Liver tissue blood flow, measured by a
laser Doppler flow meter, was kept higher in the FR-treated group than in the control group. Histologically, tissue damage was mild in the FR-treated group. The 2-day survival rate was statistically better (P < .05) in the FR-treated group than in the control group. We conclude that
FR167653 provides a protective effect for liver parenchyma and sinusoidal endothelial cells in extended liver resection with
ischemia.