Wu J, Danielsson A, Lindström P, Karlsson K, Sehlin J
Dept. of Histology and Cell Biology, University Hospital, University of Umeå, Sweden.
Scand J Gastroenterol. 1995 Jun;30(6):590-600. doi: 10.3109/00365529509089795.
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.
BB at 0.8-2.4 mM increased the lactate dehydrogenase (LDH) leakage rate dose-dependently. Pretreatment with verapamil (25-35 microM), nifedipine (35-45 microM), diltiazem (25 microM), or EGTA (1.5-5 mM) 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 microM) blocked the phenylephrine-induced calcium oscillations completely in 55% and 88% of the cells, respectively.
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.
评估了维拉帕米、硝苯地平、地尔硫䓬和乙二醇四乙酸（EGTA）对大鼠肝细胞急性溴苯（BB）毒性的保护作用，并监测了单个暴露于BB的大鼠肝细胞中的胞质[Ca2+]i。此外，研究了硝苯地平对去氧肾上腺素刺激的钙振荡的影响。
0.8 - 2.4 mM的BB剂量依赖性地增加了乳酸脱氢酶（LDH）泄漏率。用维拉帕米（25 - 35 microM）、硝苯地平（35 - 45 microM）、地尔硫䓬（25 microM）或EGTA（1.5 - 5 mM）预处理可显著减弱孵育2小时期间BB诱导（1.6 mM）的LDH泄漏率。BB未引起[Ca2+]i的任何可检测到的急性变化。BB通过阻断58%的细胞中的振荡并降低其余细胞中的振荡频率来干扰去氧肾上腺素刺激的钙振荡。硝苯地平（100和200 microM）分别在55%和88%的细胞中完全阻断了去氧肾上腺素诱导的钙振荡。
研究结果表明，维拉帕米、硝苯地平、地尔硫䓬和EGTA可显著保护大鼠肝细胞免受BB毒性。BB干扰去氧肾上腺素刺激的钙振荡。硝苯地平在高于发挥保护作用剂量时抑制振荡。
