Protective effects of calcium channel blockers in carbon tetrachloride-induced liver toxicity.
The effects of calcium channel blockers, verapamil, nifedipine and diltiazem, on CCl4-induced liver damage were determined. A single dose of CCl4 (0.5 ml/kg p.o.) led to a five-fold increase in liver calcium content. The toxic effect of CCl4 was also observed in other hepatic processes: the protein synthesis rate in the liver showed an important decrease, liver glycogen content and bile flow was decreased, and lipid peroxidation was approximately doubled. The plasma levels of cholesterol, triglycerides and transaminases (AST and ALT) also increased. When the calcium channel blockers were administered 2 hr prior to and 7 hr after the administration of the toxic agent at doses of 25 mg/kg (diltiazem) and 10 mg/kg (nifedipine and verapamil), the liver showed a significant reestablishment of several of these parameters: a considerable reduction in liver calcium content, a decrease in AST and ALT levels, and a significant increase in protein synthesis rate. There was also a partial inhibition of lipid peroxidation.
Romero
G
G
Department of Pharmacology, University of Navarra, Pamplona, Spain.
Lasheras
B
B
Sainz Suberviola
L
L
Cenarruzabeitia
E
E
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002252:Carbon Tetrachloride Poisoning / Q000150:complications*; D056486:Chemical and Drug Induced Liver Injury; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism* / Q000517:prevention & control*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D002121:Calcium Channel Blockers; D008112:Liver Glycogen; D014280:Triglycerides; D002784:Cholesterol; D002118:Calcium