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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 590-600 |
| Number of pages | 11 |
| Journal | Scandinavian Journal of Gastroenterology |
| Volume | 30 |
| Issue number | 6 |
| DOIs | |
| State | Published - 1995 |
| Externally published | Yes |
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Keywords
- Bromobenzene
- Calcium
- Diltiazem
- Hepatocyte
- Nifedipine
- Phenylephrine
- Rat
- Verapamil
ASJC Scopus subject areas
- Gastroenterology
Cite this
Protective effects of calcium channel blockers on acute bromobenzene toxicity to isolated rat hepatocytes inhibition of phenylephrine-induced calcium oscillations. / Wu, J.; Danielsson, A.; Lindström, P.; Karlsson, K.; Sehlin, J.
In: Scandinavian Journal of Gastroenterology, Vol. 30, No. 6, 1995, p. 590-600.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protective effects of calcium channel blockers on acute bromobenzene toxicity to isolated rat hepatocytes inhibition of phenylephrine-induced calcium oscillations
AU - Wu, J.
AU - Danielsson, A.
AU - Lindström, P.
AU - Karlsson, K.
AU - Sehlin, J.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - Bromobenzene
KW - Calcium
KW - Diltiazem
KW - Hepatocyte
KW - Nifedipine
KW - Phenylephrine
KW - Rat
KW - Verapamil
UR - http://www.scopus.com/inward/record.url?scp=0029070696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029070696&partnerID=8YFLogxK
U2 - 10.3109/00365529509089795
DO - 10.3109/00365529509089795
M3 - Article
C2 - 7569769
AN - SCOPUS:0029070696
VL - 30
SP - 590
EP - 600
JO - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
SN - 0036-5521
IS - 6
ER -