Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in rat

Primary graft nonfunction of steatotic liver allograft is one of the factor s causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an important contributory factor to primary graft nonfunction, In this study, we investigated the complex chain of events from transcription factor acti vation to necrosis through cytokine induction and apoptosis in steatotic ra t liver after warm I/R. Rats with alcoholic or nonalcoholic fatty liver wer e subjected to hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6 to 8 weeks developed severe hepatic necrosis accompanie d by increased neutrophil recruitment after I/R, compared with rats with no nalcoholic fatty liver or control. Hepatic apoptosis as assessed by DNA fra gmentation at 4 hours after I/R, however, increased to a similar degree in each of the 2 fatty liver models compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid increase in nuclear factor-kappa B (NF -kappa B) binding activity at 1 hour after VR, which preceded an increased expression of tumor necrosis factor alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1), In contrast, nonalcoholic fatty live r did not show such potentiation of either NF-kappa B activation or cytokin e induction after I/R. Our results have indicated that alcoholic fatty live r may differentially induce CINC-1 production and hepatic necrosis after I/ R. Furthermore, our results suggest that apoptosis per se does not always l ead to necrosis in the liver following I/R.