Evaluation of calcium channel blockers as potential hepatoprotective agents in oxidative stress injury of perfused hepatocytes

The aim of this study was to investigate the effects of calcium channel blo ckers on tertbutyl hydroperoxide (TBH) induced liver injury using isolated perfused rat hepatocytes. Rat hepatocytes were immobilized in agarose threa ds and perfused with Williams E medium. Hepatocyte injury was induced by th e addition of tertbutyl hydroperoxide(1 mM) to the perfusion medium 30 min after the addition of either verapamil or diltiazim. Hepatocyte injury was observed by monitoring the functional and metabolic competence of hepatocyt es or by ultrastructural morphological examination of hepatocytes. Verapami l (0.5 mM) reduced lactate dehydrogenase leakage in TBH-injured hepatocytes as compared to the controls (154+/-11% vs. 247+/-30%). Lipid peroxides pro duction was reduced after verapamil pretreatment as compared to the control s and oxygen consumption was increased by pretreatment of hepatocytes with verapamil. Verapamil pretreatment increased the protein synthesis activity at both levels of granular endoplasmic reticulum and free polysomes in cyto plasm and decreased ATPase activity. Diltiazem was qualitatively effective as verapamil. It is concluded that in hepatocyte oxidative injury, calcium channel blockers exhibited hepatoprotective properties. The hepatoprotectiv e effect of calcium channel blockers was accompanied by a decrease in ATPas e activity, which may implicate a normalization of Ca-1(2+), after TBH into xication.