Effects of short-term and long-term administration of amiodarone on hepatobiliary function in male rats.
Functional, biochemical and histological parameters of hepatotoxicity were assessed in male Sprague-Dawley rats receiving amiodarone (Am) short-term by gavage (5, 50, 150 and 500 mg Am kg-1 day-1, 10 days) or dietary exposure (50 ppm, 1500 ppm, 4-week duration), or by long-term dietary exposure (50 ppm, 8-month duration). Serum enzyme (ALT, AST, ICD) levels and histopathological examination indicated no observable evidence of toxicity among rats of any of the treatment groups. Reduced food intake and reduction in weight gain was observed for rats exposed short-term to 1500 ppm dietary Am. Assessment of hepatobiliary function in treated rats indicated that short-term and long-term dietary exposure to Am resulted in a compromised excretion of readily excretable phenolphthalein glucuronide (PG), although inanition may account for this effect in the 1500 ppm group. Rats receiving Am by gavage exhibited a reduction in biliary excretion of PG, which was not dose-dependent. Distribution of Am and its major metabolite, desethylamiodarone, was similar to previous reports wherein both compounds accumulated in adipose, lung and liver tissue. These data suggest that minor alterations of hepatobiliary function occur in the absence of histological alterations and may preceed biochemical changes, as assessed in this study.
Young
R A
RA
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39116-4505.
Mehendale
H M
HM
D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000503:physiopathology; D004032:Diet; D004798:Enzymes / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004798:Enzymes; D011453:Prostaglandins; D000638:Amiodarone