Chlorpromazine inhibits hepatocyte apoptosis caused by withdrawal of phenobarbital in mice.
OBJECTIVE
To study the inhibitory effect of chlorpromazine (Chl), verapamil, and aspirin on hepatocyte apoptosis induced by the cessation of phenobarbital (Phe) treatment in mice.


METHODS
Liver DNA content, ratio of liver weight/body weight, DNA fragmentation, DNA electrophoresis, the end-labeling test (TUNEL), and the morphologic changes of liver cells as indices of liver mass and hepatocyte apoptosis were applied to investigate (1) the kinetic process of hepatocyte proliferation induced by Phe 75 mg.kg-1 i.p. and the regression of hyperplastic liver caused by withdrawal of Phe in mice, (2) the effect of Chl 25 mg.kg-1, verapamil 50 mg.kg-1 or aspirin 60 mg.kg-1 i.p. on mouse hepatocyte apoptosis, and (3) the time course of effects of Chl on the regression of liver size and DNA fragmentation content after withdrawal of Phe.


RESULTS
The process of hepatocyte proliferation and regression induced by administration and withdrawal of Phe in mice consisted of 4 phases: proliferation, plateau, rapid regression, and slow regression phases. In the rapid regression phase, the typic changes of hepatocyte apoptosis were found, which was prevented in early period by the Ca(2+)-calmodulin antagonist Chl, but not by verapamil or aspirin.


CONCLUSIONS
The Ca(2+)-calmodulin played an important role in the hepatocyte apoptosis caused by withdrawal of Phe.
Eastern Institute of Hepatobiliary Surgery, Second Military Medical University, Shanghai 200438, China.
P
P
He
Z L
ZL
Yan
M C
MC
Wu
L F
LF
Li
Y J
YJ
Guo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000166:cytology*; D008297:Male; D051379:Mice; D010634:Phenobarbital; D011897:Random Allocation; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D014700:Verapamil; D001241:Aspirin; D002746:Chlorpromazine; D010634:Phenobarbital