Inhibition of tumor necrosis factor alpha gene transcription by pentoxifylline reduces normothermic liver ischemia-reperfusion injury in rats.
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 (TNFalpha) 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 TNFalpha, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured. Liver histology was assessed 6 hours after reperfusion. Liver TNFalpha mRNA was assessed by polymerase chain reaction amplification at different times after reperfusion. PTX treatment significantly decreased serum activities of TNFalpha and inhibited liver expression of TNFalpha 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 TNFalpha gene transcription, decreases serum TNFalpha levels, and reduces liver injury following normothermic I-R.
El-Ghoneimi
A
A
Laboratoire de Recherches Chirurgicales, IFR 50, Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France.
Cursio
R
R
Schmid-Alliana
A
A
Tovey
M
M
Lasfar
A
A
Michiels
J-F
JF
Rossi
B
B
Gugenheim
J
J
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000517:prevention & control*; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014665:Vasodilator Agents / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D010431:Pentoxifylline