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Scandinavian Journal of Gastroenterology Volume 30, 1995 - Issue 6
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Original Article

Protective Effects of Calcium Channel Blockers on Acute Bromobenzene Toxicity to Isolated Rat Hepatocytes Inhibition of Phenylephrine-Induced Calcium Oscillations

J. Wu Dept. of Histology and Cell Biology, Dept. of Medicine, Section for Gastroenterology and Hepatology, and Dept. of Clinical Chemistry, University Hospital, University of Umeå, Umeå, Sweden
,
Å. Danielsson Dept. of Histology and Cell Biology, Dept. of Medicine, Section for Gastroenterology and Hepatology, and Dept. of Clinical Chemistry, University Hospital, University of Umeå, Umeå, Sweden
,
P. Lindström Dept. of Histology and Cell Biology, Dept. of Medicine, Section for Gastroenterology and Hepatology, and Dept. of Clinical Chemistry, University Hospital, University of Umeå, Umeå, Sweden
,
K. Karlsson Dept. of Histology and Cell Biology, Dept. of Medicine, Section for Gastroenterology and Hepatology, and Dept. of Clinical Chemistry, University Hospital, University of Umeå, Umeå, Sweden
&
J. Sehlin Dept. of Histology and Cell Biology, Dept. of Medicine, Section for Gastroenterology and Hepatology, and Dept. of Clinical Chemistry, University Hospital, University of Umeå, Umeå, Sweden
Pages 590-600 | Received 08 Aug 1994, Accepted 10 Oct 1994, Published online: 08 Jul 2009
 
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Abstract

Background and Methods: Protective effects of verapamil, nifedipine, diltiazem, and ethylene glycol tetraacetic acid (EGTA) on acute bromobenzene (BB) toxicity to rat hepatocytes were evaluated, and cytosolic [Ca2+]i was monitored in single BB-exposed rat hepatocytes. Additionally, the effect of nifedipine on phenylephrine-stimulated calcium oscillations was investigated. Results: BB at 0.8-2.4 mM increased the lactate dehydrogenase (LDH) leakage rate dose-dependently. Pretreatment with verapamil (25-35 u.M), nifedipine (35-45 μM), diltiazem (25 μM), or EGTA (1.5-5 μM) markedly attenuated the BB-induced (1.6 mM) LDH leakage rate during 2 h of incubations. BB did not cause any detectable acute change in [Ca2+]i. BB interfered with phenylephrine-stimulated calcium oscillations, by blocking the oscillations in 58% of the cells and reducing the oscillation frequency in the rest. Nifedipine (100 and 200 μM) blocked the phenylephrineinduced calcium oscillations completely in 55% and 88% of the cells, respectively. Conclusions: The findings demonstrate that verapamil, nifedipine, diltiazem, and EGTA significantly protect rat hepatocytes against BB toxicity. BB interferes with phenylephrine-stimulated calcium oscillations. Nifedipine inhibits the oscillations at doses higher than those exerting a protective effect.

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