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

I-Hsin Lin; Ling Yang; Jeffrey W. Dalley; Tung-Hu Tsai

Biomedicine & Pharmacotherapy (Jan 2022)

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

I-Hsin Lin,
Ling Yang,
Jeffrey W. Dalley,
Tung-Hu Tsai

Affiliations

I-Hsin Lin: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Ling Yang: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Jeffrey W. Dalley: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK; Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, UK
Tung-Hu Tsai: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK; Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan; Correspondence to: Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, 155, Li-Nong Street Section 2, Taipei 112, Taiwan.

Journal volume & issue: Vol. 145
p. 112489

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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