HUMAN HEPATOCYTES ARE MORE RESISTANT THAN RAT HEPATOCYTES TO ANOXIA-REOXYGENATION INJURY

We performed this study to determine whether perfused isolated human a nd rat hepatocytes have different sensitivities to anoxia-reoxygenatio n injury. Oxygen free radicals were detected by lucigenin-enhanced che miluminescence. Lipid peroxidation was assessed by measuring malondial dehyde release. Cell injury was evaluated by measuring lactate dehydro genase release and trypan blue uptake. During the control period, luci genin-enhanced chemiluminescence, malondialdehyde and lactate dehydrog enase release and trypan blue uptake were similar in rat and human hep atocytes. During 3.5 hr of anoxia, lucigenin-enhanced chemiluminescenc e decreased to back-ground levels and malondialdehyde release remained constant in both groups. In contrast, lactate dehydrogenase release i ncreased eightfold in rat hepatocytes but only threefold in human hepa tocytes. With reoxygenation after 2.5 hr of anoxia, in rat hepatocytes lucigenin-enhanced chemiluminescence increased 13-fold within 15 min and then declined toward control levels. Malondialdehyde release doubl ed after 1 hr of reoxygenation. The rate of lactate dehydrogenase rele ase increased to a level almost twice that observed in cells kept cont inuously anoxic. In contrast, with human hepatocytes lucigenin-enhance d chemiluminescence increased only fourfold, whereas malondialdehyde a nd lactate dehydrogenase releases did not differ significantly from th ose levels measured in cells perfused continuously under anoxic condit ions. At the end of the experiment, the increase in trypan blue uptake was significantly greater with rat hepatocytes than with human hepato cytes. These results demonstrate that (a) during reoxygenation followi ng 2.5 hr of anoxia, isolated human hepatocytes generate fewer oxygen free radical, and lipoperoxides than do rat hepatocytes, and (b) human hepatocytes are more resistant to cell injury during anoxia-reoxygena tion than are rat hepatocytes.