Effects of stobadine on hypoxia and hypoxia/reoxygenation injury in isolated hepatocytes from fasted rats

Cell injury due to hypoxia and reoxygenation was investigated in the system of parenchymal hepatocytes isolated From fasted rats. The functional and s tructural integrity of hepatocytes in hypoxia was evaluated on the basis of protein synthesis and [Rb-86] release from prelabelled hepatocytes. Incuba tion of hepatocytes in nitrogen atmosphere resulted in significant inhibiti on of incorporation of [C-14]-valine into hepatocyte protein. Treatment of hepatocytes in hypoxia with the antioxidant stobadine (0.1, 1.0 and 10.0 mu M) reversed protein synthesis almost to control values. No changes were obs erved in [Rb-86] release from prelabelled hepatocytes. In the experiment wi th hypoxia/reoxygenation, hepatocytes were exposed to GO min hypoxia follow ed by 120 min reoxygenation and the injury was evaluated by lactate dehyrog enase (LD) leakage and formation of thiobarbituric acid reactive substances (TBARS). Tile addition of stobadine at the given concentrations (0.1, 1.0 and 10.0 muM) before the onset of hypoxia resulted in dose dependent protec tion from hypoxia/reoxygenation injury of isolated hepatocytes.