HYDROGEN-PEROXIDE DERIVED FROM HEPATOCYTES INDUCES SINUSOIDAL ENDOTHELIAL-CELL APOPTOSIS IN PERFUSED HYPOXIC RAT-LIVER

Background & Aims: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis, Reactive oxygen species can cause apoptosis, This study examined the hypothesis that H2O2 ind uces apoptosis in hypoxic rat liver, Methods: Blood-perfused rat liver s were made hypoxic by reducing the perfusion flow, H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electronmic roscopic methods. To evaluate the apoptosis, the liver was stained wit h the terminal deoxynucleotidyl transferase-mediated deoxyuridine trip hosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pie ces of liver in the cultured media were exposed to 0.5 mmol/L of reage nt H2O2 and stained with the TUNEL method, Results: In the hypoxic liv er, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particular ly in the midzone, All the apoptotic cells were positively stained wit h monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs), In incubated liver pieces, reagent H2O2 induced apoptosis sel ectively in SECs. Conclusions: Low-flow hypoxia induces H2O2 productio n in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the vat liver.