Pentoxifylline inhibits liver expression of tumor necrosis factor alpha mRNA following normothermic ischemia-reperfusion.
BACKGROUND
Pentoxifylline (PTX) has been shown to reduce hepatic injury after normothermic ischemia and reperfusion (I-R) in rat liver.


OBJECTIVE
The aim of this study was to evaluate the effects of PTX on liver expression of tumor necrosis factor alpha (TNFalpha) mRNA following normothermic liver I-R.


METHODS
A segmental normothermic ischemia of the liver was induced in male Lewis rats by occluding the blood vessels including the bile duct to the median and left lateral lobes for 90 min. At the end of ischemia the nonischemic liver lobes were resected. 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 min before and 60 min after induction of ischemia. Survival rates were compared and the serum activities of TNFalpha, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured. Histology of the liver was assessed 6 h after reperfusion. Liver TNFalpha mRNA was assessed by PCR amplification at 0, 60, 120, and 210 min after reperfusion.


RESULTS
PTX treatment significantly increased 7 day survival (93.3%) compared with nontreated control rats (46.6%, p<0.007). The extent of liver necrosis and the release of liver enzymes were significantly decreased after PTX treatment. Serum activities of TNFalpha were significantly decreased and liver expression of TNFalpha mRNA was inhibited after PTX treatment.


CONCLUSIONS
PTX protects the liver from ischemic injury and inhibits liver expression of TNFalpha mRNA.
El-Ghoneimi
Alaa
A
Laboratoire de Recherches Chirurgicales, Université de Nice Sophia Antipolis, Nice, France.
Cursio
Raffaele
R
Schmid-Alliana
Annie
A
Tovey
Michel
M
Lasfar
Ahmed
A
Michiels
Jean-Francois
JF
Rossi
Bernard
B
Gugenheim
Jean
J