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Effects of nicotine-specific antibodies, Nic311 and Nic-IgG, on the transfer of nicotine across the human placenta.

Abstract：

:The adverse effects of smoking during pregnancy on fetal development are, in part, due to nicotine. These effects may be due to the actions of nicotine in fetal circulation or on placental functions. In pregnant rats, vaccination with a nicotine immunogen reduces the transfer of nicotine from the maternal to fetal circulation. However, extrapolation of these results to pregnant women might not be valid due to the well-recognized differences between human and rat placentas. In the current investigation, the effects of nicotine-specific antibodies on the transfer of nicotine from the maternal to fetal circuit of the dually perfused human placental lobule were determined. Two types of nicotine-specific antibodies were investigated; nicotine-specific mouse monoclonal antibody (Nic311, K(d) for nicotine 60nM) and IgG from rabbits vaccinated with a nicotine immunogen (Nic-IgG, K(d) 1.6nM). Transfer of the antibodies from maternal to fetal circuits was negligible. Both rabbit Nic-IgG and, to a lesser extent, mouse monoclonal Nic311 significantly reduced nicotine transfer from the maternal to fetal circuit as well as the retention of the drug by placental tissue. These effects were mediated by a substantial increase in the protein binding of nicotine and a reduction in the unbound nicotine concentration. Therefore, the data cited in this report suggest that the use of nicotine-specific antibodies might reduce fetal exposure to the drug, and that antibody affinity for nicotine is a key determinant of the extent of nicotine transfer.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Nekhayeva IA,Nanovskaya TN,Pentel PR,Keyler DE,Hankins GD,Ahmed MS

doi

10.1016/j.bcp.2005.08.013

subject

Has Abstract

pub_date

2005-11-25 00:00:00

pages

1664-72

issue

11

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(05)00560-5

journal_volume

70

pub_type

杂志文章

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