In vitro study of lovastatin interactions with amiodarone and with carbon tetrachloride in isolated rat hepatocytes.
OBJECTIVE
To investigate the interactions at a metabolic level between lovastatin, amiodarone and carbon tetrachloride in isolated rat hepatocytes.


METHODS
For cell isolation two-step collagenase liver perfusion was performed. Lovastatin was administered alone in increasing concentrations (1 mumol/L, 3 mumol/L, 5 mumol/L and 10 mumol/L) and in combination with CCl(4) (86 mumol/L). The cells were also pretreated with 14 mumol/L amiodarone and then the other two compounds were added.


RESULTS
Lovastatin promoted concentration-dependent significant toxicity estimated by decrease in cell viability and GSH level by 45% and 84%, respectively. LDH-activity increased by 114% and TBARS content by 90%. CCl(4)induced the expected severe damage on the examined parameters. CCl(4) induced toxicity was attenuated after lovastatin pretreatment, which was expressed in less increased values of LDH activity and TBARS levels, as well as in less decreased cell viability and GSH concentrations. However, the pretreatment of hepatocytes with amiodarone abolished the protective effect of lovastatin.


CONCLUSIONS
We suggest that the observed cytoprotective effect was due to interactions between lovastatin, CCl(4) and amiodarone at a metabolic level.
Krasteva
A-Z
AZ
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University, 2 Dunav str., Sofia 1000, Bulgaria. adriakr@yahoo.com
Mitcheva
M-K
MK
Kondeva-Burdina
M-S
MS
Descatoire
V-A
VA
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000009:adverse effects / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D008148:Lovastatin; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D000638:Amiodarone