In vitro hepatic metabolism of a CYP3A-mediated drug, quinine, in Adelie penguins

Very little is known about Antarctic animals' ability to metabolise or detoxify xenobiotics. The activity of cytochromes P450 subfamily 3A (CYP3A) in Adelie penguin liver was studied by incubating penguin liver microsomes with a human CYP3A substrate, quinine, and results were compared with those from human liver microsomes. The mean maximum rate of metabolism (Vmax) for quinine in penguin livers was approximately five times less (160 +/- 72 versus 574 +/- 416 pmol/mg/min; P < 0.01), and the mean Km (substrate affinity) for the formation of quinine's major metabolite (3-hydroxyquinine) was significantly greater than that observed in human livers (160 +/- 73 Versus 83 +/- 19 mu M; P < 0.01). The mean intrinsic clearance (Vmax/Km) was 1.1 +/- 0.4 mu l/min (penguin), i.e. sevenfold less than in human livers (7.4 +/- 5.9 mu l/min, P < 0.005), suggesting that penguins have much less ability than humans to eliminate xenobiotics having a similar metabolic nature to quinine (i.e. CYP3A substrates). 3-Hydroxyquinine formation in penguin liver was inhibited by specific CYP3A inhibitors, midazolam and troleandomycin, but not by other CYP inhibitors, indicating that quinine metabolism to 3-hydroxyquinine in Adelie penguin liver is likely to be catalysed by a CYP isoform resembling human CYP3A. Adelie penguin liver CYP isoforms could serve as biomarkers for the impact of environmental pollution. (C) 1999 Elsevier Science Inc. All rights reserved.