TY - JOUR
T1 - Teratogenicity and Fetal-Transfer Assessment of the Retinoid X Receptor Agonist Bexarotene
AU - Takamura, Yuta
AU - Kato, Izumi
AU - Fujita-Takahashi, Manami
AU - Azuma-Nishii, Midori
AU - Watanabe, Masaki
AU - Nozaki, Rui
AU - Akehi, Masaru
AU - Sasaki, Takanori
AU - Hirano, Hiroyuki
AU - Kakuta, Hiroki
N1 - Funding Information:
This work was partially supported by the Ube Industrial Foundation (to H.K.) and JST SPRING (grant number JPMJSP2126 to Y.T.). This study was also funded in part by AIBIOS K.K. This funder was not involved in the study design, data collection, analysis, interpretation of data, writing of the article, or the decision to submit it for publication. All authors declare no other competing interests.
Publisher Copyright:
©
PY - 2022
Y1 - 2022
N2 - Bexarotene, a retinoid X receptor (RXR) agonist, is used to treat cutaneous T-cell lymphoma, and drug repositioning research has also been reported, despite warnings of teratogenicity. However, fetal transfer of bexarotene and its effect on rat fetal bone formation have not been examined. In this study, we conducted a detailed teratogenicity and fetal transferability assessment of bexarotene in rats. Repeated administration of bexarotene during pregnancy caused marked fetal atrophy and bone dysplasia. Although fetal transfer was not detectable by dynamic imaging of [11C]bexarotene by means of positron emission tomography, transfer to the fetus was confirmed by using a gamma counter. Similar levels were found in mother and fetus. In addition, we found that bexarotene was accumulated in the placenta. These findings will be useful for the toxicity assessment of bexarotene as well as for drug discovery research targeting RXR agonists, which are expected to have therapeutic effects in various diseases.
AB - Bexarotene, a retinoid X receptor (RXR) agonist, is used to treat cutaneous T-cell lymphoma, and drug repositioning research has also been reported, despite warnings of teratogenicity. However, fetal transfer of bexarotene and its effect on rat fetal bone formation have not been examined. In this study, we conducted a detailed teratogenicity and fetal transferability assessment of bexarotene in rats. Repeated administration of bexarotene during pregnancy caused marked fetal atrophy and bone dysplasia. Although fetal transfer was not detectable by dynamic imaging of [11C]bexarotene by means of positron emission tomography, transfer to the fetus was confirmed by using a gamma counter. Similar levels were found in mother and fetus. In addition, we found that bexarotene was accumulated in the placenta. These findings will be useful for the toxicity assessment of bexarotene as well as for drug discovery research targeting RXR agonists, which are expected to have therapeutic effects in various diseases.
KW - bexarotene
KW - bone dysplasia
KW - fetus transferability
KW - positron emission tomography
KW - RXR
KW - teratogenicity
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U2 - 10.1021/acsptsci.2c00126
DO - 10.1021/acsptsci.2c00126
M3 - Article
AN - SCOPUS:85136459825
SN - 2575-9108
JO - ACS Pharmacology and Translational Science
JF - ACS Pharmacology and Translational Science
ER -