APS Presentation 11:45 p.m. EDT, Sunday, April 29
Embargoed to the date and time above
Media Contact
Sarah Goodwin
(202) 249-4165 April
28-May 2
Drugs Of Abuse
Used During Pregnancy Inhibit Ability Of Human Placenta Cells To Uptake
Folate
A study using human placental
cells may help explain how drugs of abuse used during pregnancy - including
alcohol, nicotine, ecstasy, amphetamine and hashish - can produce toxic
effects on the developing fetus.
In a paper presented on April 29
at Experimental Biology 2007, in Washington, DC, researchers from the
Department of Biochemistry of the Medical Faculty in Porto University and
the Department of Gynecology and Obstetrics in S. Joao Hospital in Porto,
Portugal, reported that these substances, sometimes at doses below
“recreational” blood level, inhibited uptake of folates by cells taken from
human placenta. The presentation is part of the scientific program of The
American Physiological Society.
Folates such as folic acid play
an essential role in the synthesis of DNA and RNA and, for this reason, they
become particularly important for normal fetal development and growth.
Inadequate folic acid during early stages of fetal development increases the
risk of neural-tube defects such as anencephaly and spinal bifida. This is
why pregnant women take folic acid supplements and why many countries
supplement bread and other common foods since it is also important that
women have adequate folate levels before they conceive.
The fetus obtains folic acid
exclusively from the maternal blood, through placental transport. The
placenta has several functions, including transporting nutrients and oxygen
from the mothers' circulation to that of the fetus, eliminating waste
metabolites from fetal blood, synthesizing hormones and peptides that
support placental development and sustain pregnancy, and functioning as a
barrier to protect the fetus against the mother’s immune system. In order
to do this, the placenta must be permeable to nutrients and oxygen - but it
also is permeable to foreign compounds such as the drugs listed above.
Elisa Keating, a doctoral student
in the laboratory of Dr. Fatima Martel, examined the effect of acute (26
minutes) and chronic (48 hours) exposure of cultured human placental
cytotrophoblasts to common drugs of abuse and also to high serotonin and
glucose levels, found in the blood of mothers with preeclampsia and diabetes
respectively; anti-hypertensive drugs such as clonidine, atenolol,
alpha-methyldopa and labetalol; and insulin, used in the treatment of the
mother’s diabetes.
The good news was that both
chronic and acute exposure of the cells to insulin, serotonin, and the
majority of the prescription drugs did not seem to impair the transport of
the folates into the placental cells. However, the drugs of abuse did
inhibit the vitamin uptake, as did the acute labetalol and chronic atenolol.
Ms. Keating and Dr. Martel say
that while the results must be confirmed in in vivo studies, they do suggest
that inhibition of placental uptake of folates may be one of the mechanisms
involved in these drugs’ known toxicity to the fetus.
The work was supported by FCT and
Programa Ciencia, Tecnologia e Inovacao do Quadro Comunitario de Apoio.
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