The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone.
Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group) consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v) ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase) from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption) was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.
Ito
D T
DT
Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Av. Dr. Enéas C. Aguiar, 05403-000 São Paulo, SP, Brazil.
Molina
H M
HM
Andriolo
A
A
Borges
D R
DR
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D010101:Oxygen Consumption; D010477:Perfusion; D011758:Pyrroles / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013448:Sulfobromophthalein / Q000493:pharmacokinetics
D015415:Biomarkers; D006538:Heptanoic Acids; D011758:Pyrroles; D013448:Sulfobromophthalein; D000431:Ethanol; D000069059:Atorvastatin; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase