Intralobular heterogeneity of oxidative stress and cell death in ischemia-reperfused rat liver

The relationship between zonal oxidative stress and cell death after ischemia-reperfusion injury in rat liver was investigated. Oxidative stress was detected in situ by perfusion with nitroblue tetrazolium, which is converted to insoluble blue formazan by reducting agents. Cell death was detected in situ by perfusion with trypan blue. When isolated liver was perfused after 30 or 60 min of warm ischemia, oxidative stress was detected in periportal parenchymal cells after 30 min of reperfusion. It spread in the shape of a doughnut to midzonal cells after 60 min of reperfusion. On the other hand, cell death was observed in parenchymal cells that were within the doughnut-like area in which oxidative stress was detected. The extent of oxidative stress and cell death was higher after 60 min of ischemia than after 30 min of ischemia. In nonparenchymal cells, oxidative stress was observed in midzonal and pericentral regions after only 12 min of reperfusion, but minor cell death was observed only in periportal and midzonal regions after 30 min of reperfusion. Administration of allopurinol, an inhibitor of xanthine oxidase, suppressed oxidative stress and cell death in periportal parenchymal cells. These findings indicate that periportal and midzonal parenchymal cell death can be caused by zone-specific and xanthine-oxidase-mediated oxidative stress in parenchymal cells.