Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity

The Journal of Toxicological Sciences
Norie MurayamaHiroshi Yamazaki

Abstract

Evidence has been presented for auto-induced human cytochrome P450 3A enzyme involvement in the teratogenicity and clinical outcome of thalidomide due to oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers. In this study, more relevant human placenta preparations and placental BeWo cells showed low but detectable P450 3A4/5 mRNA expression and drug oxidation activities. Human placental microsomal fractions from three subjects showed detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. Human placental BeWo cells, cultured in the recommended media, also indicated detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. To reduce any masking effects by endogenous hormones used in the recommended media, induction of P450 3A4/5 mRNA and oxidation activities were measured in placental BeWo cells cultured with a modified medium containing 5% charcoal-stripped fetal bovine serum. Thalidomide significantly induced P450 3A4/5, 2B6, and pregnane X receptor (PXR) mRNA levels 2 to 3-fold, but rifampicin only enhanced P450 3A5 and PXR mRNA under the modified media conditions. Under these modified conditions, thalidomide also significantly induced ...Continue Reading

References

Apr 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·G B GordonV Balasubramanian
Aug 1, 1993·The Journal of Clinical Investigation·J D SchuetzP S Guzelian
Jul 8, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Caroline Prouillac, Sylvaine Lecoeur
Oct 22, 2011·Placenta·V L GeenesC Williamson
Dec 12, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ioannis PapageorgiouJashvant D Unadkat
Dec 20, 2013·Chemical Research in Toxicology·Goutam ChowdhuryF Peter Guengerich
Jan 28, 2014·Chemical Research in Toxicology·Norie MurayamaHiroshi Yamazaki
Feb 21, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kanako YajimaHiroshi Yamazaki
Feb 24, 2016·Scientific Reports·Yasuhiro KazukiMitsuo Oshimura

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Citations

Mar 20, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Benjamin A ElserHanna E Stevens
Mar 5, 2020·Expert Review of Clinical Pharmacology·Ricardo Blanco-CastañedaMartha Sosa-Macías
Sep 7, 2021·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Edson Santos Ferreira-FilhoIsabel Cristina Esposito Sorpreso

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