ArticleThe Journal of toxicological sciences2017
Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity.
Article in The Journal of toxicological sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 13 citations in OpenAlex.
- Article
- Article
- Augmentation of Pectoral Fin Teratogenicity by Thalidomide in Human Cytochrome P450 3A-Expressing Zebrafish.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Combined Maternal Exposure to Cypermethrin and Stress Affect Embryonic Brain and Placental Outcomes in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Phase 0 of the Xenobiotic Response: Nuclear Receptors and Other Transcription Factors as a First Step in Protection from Xenobiotics.Nuclear receptor research · 2019Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
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 midazolam 1´-hydroxylation and thalidomide 5-hydroxylaion activities 3-fold but not bupropion hydroxylation activity. Taken together, activation of thalidomide to 5-hydroxythalidomide with autoinduction of P450 3A enzymes in human placentas, as well as livers, is suggested in vivo.
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Registered trials
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