Nicotine metabolism in pregnant and nonpregnant rabbits

Tutka, Piotr; Dempsey, Delia; Jacob, Peyton; Benowitz, Neal L.; Kroetz, Deanna L.

doi:10.1080/14622200802238878

Cited by 4 publications

(1 citation statement)

References 21 publications

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“…This is consistent with in vitro findings of very little CYP2A6 activity in the placenta. Low glucuronidation activity has been detected in the placenta, but it is not clear whether the UGT2B10 isoform is present (Collier et al, 2002;Tutka et al, 2008). The observation that NIC crosses the placenta with little evidence of metabolism to COT suggests that placenta is unlikely to be a major contributor to higher NIC metabolism in pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Influence of Pregnancy on Nicotine Metabolic Pathways

Taghavi

Arger

Heil

et al. 2017

J Pharmacol Exp Ther

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Nicotine metabolism increases in pregnancy, which may contribute to the difficulties that pregnant women have in quitting smoking. We aimed to determine the extent and timing of changes in nicotine metabolic pathways, including C-oxidation, N-glucuronidation, and the pregnancy-induced influences on the activity of enzymes mediating these pathways (CYP2A6 and UGT2B10, respectively). Current smoking pregnant women ( = 47) provided a urine sample during early pregnancy (12.5 weeks), late pregnancy (28.9 weeks), and 6 months postpartum. Concentrations of urinary nicotine and metabolites were analyzed using liquid chromatography tandem mass spectrometry and compared using general linear repeated measures analyses. Nicotine C-oxidation was 1.07-fold ( = 0.12) and 1.11-fold ( < 0.001) higher at early and late pregnancy, respectively, compared with postpartum. Nicotine N-glucuronidation was 1.33-fold ( = 0.06) and 1.67-fold ( = 0.003) higher at early and late pregnancy, respectively, compared with postpartum. The CYP2A6 phenotype ratio (total 3'-hydroxycotinine/cotinine) was significantly higher at early and late pregnancy compared with postpartum (all < 0.05) and correlated with nicotine C-oxidation (all < 0.001), suggesting CYP2A6 activity is induced during pregnancy. The UGT2B10 phenotype ratio (nicotine glucuronide/nicotine) was higher at early and late pregnancy compared with postpartum ( = 0.07 and < 0.05, respectively) and correlated with a second UGT2B10 phenotype ratio (cotinine glucuronide/cotinine) (all < 0.001), suggesting UGT2B10 activity is induced during pregnancy. In conclusion, pregnancy-induced increases in nicotine metabolism start by 12 weeks gestation and continue as pregnancy progresses most likely due to induction of CYP2A6 and UGT2B10, resulting in potential reductions in the effectiveness of nicotine replacement therapies and an increase in metabolism of other CYP2A6 and UGT2B10 substrates during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Longitudinal Influence of Pregnancy on Nicotine Metabolic Pathways

Taghavi

Arger

Heil

et al. 2017

J Pharmacol Exp Ther

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In-utero exposure to nicotine alters the development of the rabbit cardiac conduction system and provides a potential mechanism for sudden infant death syndrome

et al. 2017

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In-utero exposure to tobacco smoke remains the highest risk factor for sudden infant death syndrome (SIDS). To alleviate the risks, nicotine replacement therapies are often prescribed to women who wish to quit smoking during their pregnancy. Cardiac arrhythmias is considered the final outcome leading to sudden death. Our goal in this study was to determine if exposing rabbit fetus to nicotine altered the cardiac conduction system of newborn kittens in a manner susceptible to cause SIDS. Using neuronal markers and a series of immunohistological and electrophysiological techniques we found that nicotine delayed the development of the cardiac pacemaker center (sinoatrial node) and decreased its innervation. At the molecular level, nicotine favored the expression of cardiac sodium channels with biophysical properties that will tend to slow heart rate and diminish electrical conduction. Our results show that alterations of the cardiac sodium current may contribute to the bradycardia, conduction disturbances and other cardiac arrhythmias often associated to SIDS and raise awareness on the use of replacement therapy during pregnancy.

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