Hepatic ischemia-reperfusion injury is a major cause of post-operative hepatic dysfunction and liver failure after transplantation. Mitochondrial pathways can be either beneficial or detrimental to hepatic cell apoptosis during hepatic ischemia/reperfusion injury, depending on multiple factors. Hepatic ischemia/reperfusion injury may be induced by opened mitochondrial permeability transition pore, released apoptosis-related proteins, up-regulated B-cell lymphoma-2 gene family proteins, unbalanced mitochondrial dynamics, and endoplasmic reticulum stress, which are integral parts of mitochondrial pathways. In this review, we discuss the role of mitochondrial pathways in apoptosis that account for the most deleterious effect of hepatic ischemia/reperfusion injury.

The aim of the present study was to explore the mechanism underlying the effects of a selective liver nitric oxide (NO) donor, O-vinyl1-(pyrrolidin-1-yl)-diazen-1-ium-1,2-diolate (V-PYRRO/NO), on the gene expression of leukotriene C4 synthase (LTC4S) during hepatic ischemia/reperfusion (I/R). Adult male Sprague-Dawley rats were divided into 3 groups: Sham (control), I/R and V-PYRRO/NO + I/R groups. The liver was subjected to 1 h of partial hepatic ischemia followed by 5 h of reperfusion, saline or V-PYRRO/NO (1.06 µmol/kg/h) administered intravenously. The mRNA expression levels of LTC4S in rat liver tissue were examined by the reverse transcription-polymerase chain reaction method, the protein expression levels of nuclear factor-κB (NF-κB) p65, p50 and IκBα in liver cell lysates and nuclear extracts were detected by western blot analysis. Hepatic mRNA expression of LTC4S was lower in V-PYRRO/NO + I/R group compared to the I/R group. In addition, the protein expression levels of NF-κB p65 and p50 in the nucleus extract were lower in the V-PYRRO/NO + I/R group when compared with the I/R group. However, the IκBα protein in the 3 groups was not changed. Immunohistochemistry staining revealed that the I/R liver exhibited strong cytoplasmic and nuclear staining for NF-κB p65; however, the V-PYRRO/NO + I/R group liver presented slight cytoplasmic and nuclear staining. In conclusion, V-PYRRO/NO may downregulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκBα during hepatic I/R injury.