Trans-placental transfer of nicotine: Modulation by organic cation transporters

Nicotine is a highly addictive substance and harmful to the developing foetus. However, few studies have investigated the transporter mechanism responsible for regulating the transfer of nicotine across the blood-placental interface. A multiple in-vivo microdialysis system coupled to ultra-high-perf...

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Autores principales:	I-Hsin Lin, Ling Yang, Jeffrey W. Dalley, Tung-Hu Tsai
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Nicotine In-vivo microdialysis Blood-placental barrier Transplacental transfer Pharmacokinetics Organic cation transporter Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a1c7371bf1a14f9da163afd6cc304b31
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spelling	oai:doaj.org-article:a1c7371bf1a14f9da163afd6cc304b312021-12-04T04:33:06ZTrans-placental transfer of nicotine: Modulation by organic cation transporters0753-332210.1016/j.biopha.2021.112489https://doaj.org/article/a1c7371bf1a14f9da163afd6cc304b312022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221012750https://doaj.org/toc/0753-3322Nicotine is a highly addictive substance and harmful to the developing foetus. However, few studies have investigated the transporter mechanism responsible for regulating the transfer of nicotine across the blood-placental interface. A multiple in-vivo microdialysis system coupled to ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed to monitor simultaneously nicotine and cotinine in the blood, placenta, foetus, and amniotic fluid of pregnant rats. The pharmacological mechanism of nicotine transfer across the placenta was investigated by co-administering corticosterone, an inhibitor of organic cation transporters (OCTs) that partly mediate the exchange of nicotine across the placenta. The results revealed that intravenously administered nicotine (1 mg/kg) was rapidly metabolised to cotinine with a transformation ratio (AUCcotinine/AUCnicotine) of 0.67 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.12, 0.31 ± 0.05 in maternal blood, placenta, amniotic fluid, and foetus, respectively. The tissue transformation ratios (AUCtissue/AUCblood) were 0.83 ± 0.16, 0.65 ± 0.17, 0.57 ± 0.13 for nicotine, and 0.25 ± 0.06, 0.24 ± 0.12, 0.26 ± 0.04 for cotinine at placenta, amniotic fluid and foetus, respectively. Following the co-administration of corticosterone (2 mg/kg), the tissue transformation ratio of nicotine was significantly reduced in the placenta but was significantly increased in the foetus. Levels of cotinine were not significantly altered by the administration of corticosterone. These findings implicate OCT in mediating the transfer of nicotine across the blood-placenta barrier. Understanding the mechanism of nicotine transfer through the placenta may inform therapeutic strategies to lessen the exposure of the developing foetus to nicotine in the maternal bloodstream.I-Hsin LinLing YangJeffrey W. DalleyTung-Hu TsaiElsevierarticleNicotineIn-vivo microdialysisBlood-placental barrierTransplacental transferPharmacokineticsOrganic cation transporterTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112489- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nicotine In-vivo microdialysis Blood-placental barrier Transplacental transfer Pharmacokinetics Organic cation transporter Therapeutics. Pharmacology RM1-950
spellingShingle	Nicotine In-vivo microdialysis Blood-placental barrier Transplacental transfer Pharmacokinetics Organic cation transporter Therapeutics. Pharmacology RM1-950 I-Hsin Lin Ling Yang Jeffrey W. Dalley Tung-Hu Tsai Trans-placental transfer of nicotine: Modulation by organic cation transporters
description	Nicotine is a highly addictive substance and harmful to the developing foetus. However, few studies have investigated the transporter mechanism responsible for regulating the transfer of nicotine across the blood-placental interface. A multiple in-vivo microdialysis system coupled to ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed to monitor simultaneously nicotine and cotinine in the blood, placenta, foetus, and amniotic fluid of pregnant rats. The pharmacological mechanism of nicotine transfer across the placenta was investigated by co-administering corticosterone, an inhibitor of organic cation transporters (OCTs) that partly mediate the exchange of nicotine across the placenta. The results revealed that intravenously administered nicotine (1 mg/kg) was rapidly metabolised to cotinine with a transformation ratio (AUCcotinine/AUCnicotine) of 0.67 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.12, 0.31 ± 0.05 in maternal blood, placenta, amniotic fluid, and foetus, respectively. The tissue transformation ratios (AUCtissue/AUCblood) were 0.83 ± 0.16, 0.65 ± 0.17, 0.57 ± 0.13 for nicotine, and 0.25 ± 0.06, 0.24 ± 0.12, 0.26 ± 0.04 for cotinine at placenta, amniotic fluid and foetus, respectively. Following the co-administration of corticosterone (2 mg/kg), the tissue transformation ratio of nicotine was significantly reduced in the placenta but was significantly increased in the foetus. Levels of cotinine were not significantly altered by the administration of corticosterone. These findings implicate OCT in mediating the transfer of nicotine across the blood-placenta barrier. Understanding the mechanism of nicotine transfer through the placenta may inform therapeutic strategies to lessen the exposure of the developing foetus to nicotine in the maternal bloodstream.
format	article
author	I-Hsin Lin Ling Yang Jeffrey W. Dalley Tung-Hu Tsai
author_facet	I-Hsin Lin Ling Yang Jeffrey W. Dalley Tung-Hu Tsai
author_sort	I-Hsin Lin
title	Trans-placental transfer of nicotine: Modulation by organic cation transporters
title_short	Trans-placental transfer of nicotine: Modulation by organic cation transporters
title_full	Trans-placental transfer of nicotine: Modulation by organic cation transporters
title_fullStr	Trans-placental transfer of nicotine: Modulation by organic cation transporters
title_full_unstemmed	Trans-placental transfer of nicotine: Modulation by organic cation transporters
title_sort	trans-placental transfer of nicotine: modulation by organic cation transporters
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/a1c7371bf1a14f9da163afd6cc304b31
work_keys_str_mv	AT ihsinlin transplacentaltransferofnicotinemodulationbyorganiccationtransporters AT lingyang transplacentaltransferofnicotinemodulationbyorganiccationtransporters AT jeffreywdalley transplacentaltransferofnicotinemodulationbyorganiccationtransporters AT tunghutsai transplacentaltransferofnicotinemodulationbyorganiccationtransporters
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Trans-placental transfer of nicotine: Modulation by organic cation transporters

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