New evidence for the role of TNF-α in liver ischaemic/reperfusion injury
2008
Background Tumour necrosis factor-alpha (TNF-α) plays a key role in causing ischaemia/reperfusion (I/R) injury. I/R also causes activation of xanthine oxidase and dehydrogenase (XDH + XO) system that, via generated free radicals, causes organ damage. We investigated the effect of ischaemia, reperfusion and non-ischaemic prolonged perfusion (NIP) on TNF-α and XDH + XO production in an isolated perfused rat liver model.
Materials and methods Rat livers underwent 150 min NIP (control group) or two hours of ischaemia followed by reperfusion (I/R group). TNF-α (TNF-α mRNA and protein level), XDH + XO production and bile secretion were determined in tissue and effluent at baseline, at 120 min of ischaemia, after 30 min of reperfusion (I/R group) and after 120 and 150 min of prolonged perfusion (control).
Results Unexpectedly, neither ischaemia nor reperfusion had any effect on TNF-α production. TNF-α in effluent was 11 ± 4·8 pg mL−1 at baseline, 7 ± 3·2 pg mL−1 at the end of ischaemia, and 13 ± 5·3 pg mL−1 after 30 min of reperfusion. NIP, however, caused a significant increase of TNF-α synthesis and release. TNF-α effluent level after 120 and 150 min of perfusion was 392 ± 78·7 pg mL−1 and 408 ± 64·3 pg mL−1, respectively. TNF-α mRNA in tissue was also significantly elevated compared to baseline levels (1·31 ± 0·2 P < 0·001 and 1·38 P < 0·002, respectively). Decrease of liver function (expressed by bile secretion) during I/R and NIP was accompanied by significant XDH + XO elevation.
Conclusion This is the first evidence that NIP, and not I/R, is the decisive trigger for TNF-α production. This study leads to a better understanding of pathogenesis of liver I/R and perfusion damage.
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