Effect of leflunomide pretreatment on Kupffer cells in transplanted rat liver

AIM To study the effect of leflunomide on rat liver Kupffer cells before liver transplantion. METHODS SD rats were used as donors and recipients to build orthotopic liver transplantation models. The recipient rats were pretreated by a 3 day course of 1% carboxymethylcellulose (1ml/day, PO) in control group or leflunomide (10mg/kg·d, PO) in treatment group. Blood and liver samples were taken at 1, 2, 3 and 24 hours respectively after transplantation. Levels of TNF and ALT in serum, and MDA in liver tissues were measured, ultrastructure of liver and one week survival rates observed. RESULTS The levels of serum TNF (5 3kU/L±0 41kU/L) and MDA in liver tissues (484 6nmol/g±23 6nmol/g) increased rapidly, and TNF expression was strongly positive 3 hours after transplantation in control group. The Lef pretreated recipients had little changes in serum TNF levels (0 9kU/L±0 11kU/L) and MDA in liver tissues (361 8nmol/g±15 4nmol/g), and TNF expression was negative, with a significant difference between the two groups ( P 0 01). The Kupffer cells from controls were activated in appearance, while those from pretreated group showed no evidence of activation under electron microscope. One week survival rates for control and treatment groups were 0% and 60%, respectively. CONCLUSION Leflunomide pretreatment can suppress TNF and O 2 production and the activation of Kupffer cells in liver transplantation model, thus minimizing cold ischemic reperfusion injury.