title: Liver histopathology and liver and serum alanine aminotransferase and alkaline phosphatase activities in epileptic dogs receiving phenobarbital.
abstract: Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.
authors.affiliation: Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, 550 University Avenue, Charlottetown, Prince Edward Island, C1A 4P3, Canada. cgaskill@upei.ca
authors.forename: C L
authors.initials: CL
authors.lastname: Gaskill
authors.forename: L M
authors.initials: LM
authors.lastname: Miller
authors.forename: J S
authors.initials: JS
authors.lastname: Mattoon
authors.forename: W E
authors.initials: WE
authors.lastname: Hoffmann
authors.forename: S A
authors.initials: SA
authors.lastname: Burton
authors.forename: H C J
authors.initials: HC
authors.lastname: Gelens
authors.forename: S L
authors.initials: SL
authors.lastname: Ihle
authors.forename: J B
authors.initials: JB
authors.lastname: Miller
authors.forename: D H
authors.initials: DH
authors.lastname: Shaw
authors.forename: A E
authors.initials: AE
authors.lastname: Cribb
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D004283:Dog Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D004285:Dogs; D004790:Enzyme Induction / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy / Q000662:veterinary*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000662:veterinary; D008297:Male; D010634:Phenobarbital / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D010634:Phenobarbital