The effect of co-administration of simvastatin and alcohol in rats.
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.
Kolovou
Genovefa D
GD
Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave, 176 74 Athens, Greece. g-kolovou@yahoo.co.uk
Mikhailidis
D P
DP
Daskalova
Deliana C
DC
Kafaltis
Nikolaos
N
Adamopoulou
Evdokia N
EN
Malakos
John
J
Bilianou
Helen G
HG
Theocharis
Stamatious E
SE
Pilatis
Nectarios D
ND
Mykoniatis
Michael G
MG
Cokkinos
Dennis V
DV
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
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