Physiol. Res. 49: 261-268, 2000

Evaluation of Calcium Channel Blockers as Potential Hepatoprotective Agents in Oxidative Stress Injury of Perfused Hepatocytes

H. FARGHALI, E. KMONÍČKOVÁ, H. LOTKOVÁ1, J. MARTÍNEK2

Institute of Pharmacology and 2Institute of Histology and Embryology, First Faculty of Medicine, Charles University, Prague, and 1Department of Physiology, Faculty of Medicine, Charles University, Hradec Králové, Czech Republic

Received June 15, 1999
Accepted August 5, 1999


Summary
The aim of this study was to investigate the effects of calcium channel blockers on tertbutyl hydroperoxide (TBH) induced liver injury using isolated perfused rat hepatocytes. Rat hepatocytes were immobilized in agarose threads and perfused with Williams E medium. Hepatocyte injury was induced by the 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 hepatocytes or by ultrastructural morphological examination of hepatocytes. Verapamil (0.5 mM) reduced lactate dehydrogenase leakage in TBH-injured hepatocytes as compared to the controls (154± 11 % vs. 247± 30 %). Lipid peroxides production was reduced after verapamil pretreatment as compared to the controls 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 cytoplasm 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 hepatoprotective effect of calcium channel blockers was accompanied by a decrease in ATPase activity, which may implicate a normalization of Ca2+i after TBH intoxication.


Key words
Verapamil · Diltiazem · Tertbutyl hydroperoxide · Hepatoprotection · ATPase

Reprint requests
H. Farghali, Institute of Pharmacology, First Faculty of Medicine, Charles University, Albertov 4, 128 00 Prague 2, Czech Republic. e-mail: hfarg@lf1.cuni.cz

© 2000 by the Institute of Physiology, Czech Academy of Sciences