Acetaminophen UDP-glucuronosyltransferase in ferrets: species and gender differences, and sequence analysis of ferret UGT1A6

Journal of Veterinary Pharmacology and Therapeutics
Michael H Court

Abstract

The principal objective of this study was to determine whether ferrets glucuronidate acetaminophen more slowly compared with other species, and if so investigate the molecular basis for the difference. Acetaminophen-UDP-glucuronosyltransferase (UGT) activities were measured using hepatic microsomes from eight ferrets, four humans, four cats, four dogs, rat, mouse, cow, horse, monkey, pig and rabbit. Gender differences between male and female ferret livers were explored using enzyme kinetic analysis. Immunoblotting of microsomal proteins was also performed using UGT-specific antibodies. Finally, the exon 1 region of UGT1A6, a major acetaminophen-UGT, was sequenced. Glucuronidation of acetaminophen was relatively slow in ferret livers compared with livers from all other species except cat. Gender differences were also apparent, with intrinsic clearance (Vmax/Km) values significantly higher in male compared with female ferret livers. Furthermore, Vmax values correlated with densitometric measurements of two protein bands identified with a UGT1A subfamily-specific antibody. No deleterious mutations were identified in the exon 1 or flanking regions of the ferret UGT1A6 gene. In conclusion, like cats, ferret livers glucuronidate acet...Continue Reading

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Citations

Sep 15, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Joanna M RedmonMichael H Court
Jul 17, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Mayu KakehiMayumi Ishizuka
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Oct 11, 2017·The Journal of Pharmacy and Pharmacology·Novera AlamDavid J Greenblatt
Feb 5, 2019·Drug Metabolism Reviews·Aline T MarinhoSofia A Pereira
May 29, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hirotada ShirataniTsuyoshi Yokoi
Mar 8, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S KrishnaswamyM H Court
Nov 19, 2010·Journal of Veterinary Pharmacology and Therapeutics·S Modric, M Martinez
Nov 6, 2015·Journal of Veterinary Pharmacology and Therapeutics·K KusanoS Nagata
Mar 3, 2017·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Hazuki MizukawaMayumi Ishizuka
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Sep 22, 2010·Biochemical Pharmacology·M Cristina de AlmagroCarlos J Ciudad
Nov 16, 2010·The Veterinary Clinics of North America. Exotic Animal Practice·Hugo van OostromJoost J Uilenreef

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