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
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