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. AIM 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. MATERIALS AND 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. CONCLUSION PTX protects the liver from ischemic injury and inhibits liver expression of TNFalpha mRNA.

[1]  N. Selzner,et al.  Protective strategies against ischemic injury of the liver. , 2003, Gastroenterology.

[2]  Y. Kihara,et al.  Beneficial effects of pentoxifylline and propentofylline on the warm ischemic injury of rat livers. , 2002, Transplantation proceedings.

[3]  A. Aslan,et al.  Pentoxifylline Contributes to the Hepatic Cytoprotective Process in Rats Undergoing Hepatic Ischemia and Reperfusion Injury , 2001, European Surgical Research.

[4]  J. Mouiel,et al.  Improvement of normothermic rat liver ischemia/reperfusion by muramyl dipeptide. , 1998, The Journal of surgical research.

[5]  Y. Yamaoka,et al.  Efficiency of pentoxifylline in donor pretreatment in rat liver transplantation. , 1997, The Journal of surgical research.

[6]  G. Klintmalm,et al.  Effect of pentoxifylline on hepatic ischemia and reperfusion injury. , 1997, Surgery.

[7]  J. Lemasters,et al.  PROTECTION BY PENTOXIFYLLINE AGAINST NORMOTHERMIC LIVER ISCHEMIA/REPERFUSION IN RATS , 1995, Transplantation.

[8]  C. Esquivel,et al.  Pentoxifylline inhibits production of superoxide anion and tumor necrosis factor by Kupffer cells in rat liver preservation. , 1993, Transplantation proceedings.

[9]  H. Fusamoto,et al.  Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat , 1992, Hepatology.

[10]  Z. Ba,et al.  Mechanism of the beneficial effects of pentoxifylline on hepatocellular function after trauma hemorrhage and resuscitation. , 1992, Surgery.

[11]  J. Norton,et al.  Pentoxifylline suppression of tumor necrosis factor gene transcription. , 1991, Surgery.

[12]  M. Edwards,et al.  Pentoxifylline inhibits interleukin-2-induced leukocyte-endothelial adherence and reduces systemic toxicity. , 1991, Surgery.

[13]  G. Gores,et al.  LEUKOCYTE ADHESION AND CELL DEATH FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION IN THE RAT , 1991, Transplantation.

[14]  H. Jaeschke,et al.  Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. , 1991, The American journal of physiology.

[15]  R. Strieter,et al.  Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. , 1990, The Journal of clinical investigation.

[16]  Y. Chrétien,et al.  Protective effect of vasodilators on liver function after long hypothermic preservation: A study in the isolated perfused rat liver , 1989, Hepatology.

[17]  R. Strieter,et al.  Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxofylline , 1988 .

[18]  Y. Kawashima,et al.  Blood level of mitochondrial aspartate aminotransferase as an indicator of the extent of ischemic necrosis of the rat liver , 1986, Hepatology.

[19]  W. Fiers,et al.  Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Cerami,et al.  Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[21]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[22]  H. Rüdiger,et al.  Tumor necrosis factor alpha, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver. , 2002, Gastroenterology.

[23]  B. Hultberg,et al.  Acute ischemic liver failure in the rat: a reproducible model not requiring portal decompression. , 1989, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.

[24]  H. Schlayer,et al.  Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase. , 1988, Journal of hepatology.