Calcium channel blocking agents protect against acetaminophen-induced cytotoxicity in rat hepatocytes.
The effect on acetaminophen-induced cytotoxicity of three calcium channel blocking agents--diltiazem, verapamil and gallopamil--was studied in primary cultures of rat hepatocytes and compared with the chelating agent EGTA. Using the measurement of cytosolic lactate dehydrogenase (LDH) as an index of cytotoxicity, it was demonstrated that a 1-hr pretreatment with calcium channel blocking agents protected cells against acetaminophen cytotoxicity, but were less effective than EGTA. These data suggest that influx of extracellular Ca2+ into the cells could have a role in the genesis of hepatocyte injury by acetaminophen.
Thibault
N
N
Laboratoire de Toxicologie, Faculté de Pharmacie, Paris, France.
Peytavin
G
G
Claude
J R
JR
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D000082:Acetaminophen