Inhibition of Tumor Necrosis Factor Alpha Gene Transcription by Pentoxifylline Reduces Normothermic Liver Ischemia-Reperfusion Injury in Rats

Abstract 

Pentoxifylline (PTX) has been shown to protect the liver against normothermic ischemia-reperfusion (I-R) injury. The aims of this study were to investigate the action of PTX on tumor necrosis factor alpha (TNFα) gene transcription following normothermic liver I-R as well as to evaluate the resulting effects on liver function and survival. A segmental normothermic liver ischemia was induced for 90 minutes. Rats were divided into three groups: group 1, control, Ringer lactate administration; group 2, PTX treatment; group 3, sham-operated control rats. PTX (50 mg/kg) was injected intravenously 30 minutes before induction of ischemia and 30 minutes before reperfusion. The nonischemic liver lobes were resected at the end of ischemia. Survival rates were compared and serum activities of TNFα, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured. Liver histology was assessed 6 hours after reperfusion. Liver TNFα mRNA was assessed by polymerase chain reaction amplification at different times after reperfusion. PTX treatment significantly decreased serum activities of TNFα and inhibited liver expression of TNFα mRNA. The extent of liver necrosis and serum levels of liver enzymes were significantly decreased by PTX treatment, resulting in a significant increase in 7-day survival compared with nontreated control rats. In conclusion, PTX inhibits liver TNFα gene transcription, decreases serum TNFα levels, and reduces liver injury following normothermic I-R.