title: The effect of co-administration of simvastatin and alcohol in rats.
abstract: BACKGROUND
  The effect of chronic co-administration of alcohol (Alc) and lipid-lowering drugs on hepatic function has not been extensively evaluated. We studied the effects of administering Alc together with a 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitor [simvastatin (S)].
  
  
  METHODS
  Male Wistar rats (8 weeks old) were randomized and divided into 4 groups of 10 each. They were fed (once a day) via a stomach tube with: 1) 2 ml of olive oil; group Oil, 2) with Oil + 2 ml of 25% v/v pure Alc in water; group Alc + Oil, 3) with Oil + S (65 micrograms/100 g body weight); group S + Oil, 4) with Oil + Alc + S; group S + Alc + Oil. Another 13 male Wistar rats were only fed a standard laboratory diet (control group). After 8 weeks blood samples were drawn and the livers were removed. Blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total protein, albumin, total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed.
  
  
  RESULTS
  Differences were found between the control group and tube-fed groups in glucose (p < 0.001). No differences were found among tube-fed groups in blood glucose, ALT, total protein, albumin, AP and TC. AST activity was significantly higher in the Alc + Oil than in the Oil or S + Oil groups (p < 0.001 for both comparisons) demonstrating the effect of Alc on AST. The AST did not differ significantly in the Oil or S + Oil groups indicating a lack of effect of S. Furthermore, S significantly reduced the Alc-induced increase in AST (Alc + Oil vs S + Alc + Oil; p = 0.042). The TG concentration was significantly higher in the Alc + Oil group compared to the Oil, S + Oil and S + Alc + Oil groups (p = 0.02). Therefore, S significantly decreased the alcoholinduced increase in TG. Liver histopathology was similar in all groups and within the normal range.
  
  
  CONCLUSIONS
  A moderate amount of Alc daily together with S is safe in rats. Additionally, S administration in Wistar rats diminishes the Alc-induced TG and AST rises.
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave, 176 74 Athens, Greece. g-kolovou@yahoo.co.uk
authors.forename: Genovefa D
authors.initials: GD
authors.lastname: Kolovou
authors.forename: D P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: Deliana C
authors.initials: DC
authors.lastname: Daskalova
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kafaltis
authors.forename: Evdokia N
authors.initials: EN
authors.lastname: Adamopoulou
authors.forename: John
authors.initials: J
authors.lastname: Malakos
authors.forename: Helen G
authors.initials: HG
authors.lastname: Bilianou
authors.forename: Stamatious E
authors.initials: SE
authors.lastname: Theocharis
authors.forename: Nectarios D
authors.initials: ND
authors.lastname: Pilatis
authors.forename: Michael G
authors.initials: MG
authors.lastname: Mykoniatis
authors.forename: Dennis V
authors.initials: DV
authors.lastname: Cokkinos
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001798:Blood Proteins / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D001786:Blood Glucose; D001798:Blood Proteins; D002492:Central Nervous System Depressants; D012709:Serum Albumin; D014280:Triglycerides; D000431:Ethanol; D002784:Cholesterol; D019821:Simvastatin; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase