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Binding of acetaldehyde to human and Guinea pig placentae in vitro
Marjie L Hard1, Umar Iqbal, James F Brien
1Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children and Department of Pharmaceutical Sciences, University of Toronto, Ontario, Canada.
Background:
Significant interindividual variability exists following maternal alcohol consumption; not all children born to alcoholic women manifest the symptoms associated with foetal alcohol spectrum disorder (FASD).
Objective:
To investigate the potential role of the placenta as a source of variability by determining if interindividual variability exists in the binding of acetaldehyde to human placenta.
Methods:
Acetaldehyde was added to ten different human placental homogenates and subjected to equilibrium dialysis. Homogenates of placentae obtained from guinea pigs chronically exposed to ethanol throughout gestation were also dialysed in the presence of acetaldehyde to look for alterations in binding after chronic alcohol exposure. Nonlinear least-squares regression analysis was used to characterize the binding system involved.
Results:
It was found that the amount of acetaldehyde bound to human placentae varied by as much as 3-fold among placentae. The binding profile of acetaldehyde was characterized as a two site binding system (Ka(1)=9.8 x 10(5)+/-0.7 x 10(5)l/mol, N(1)=1.1 x 10(-8)+/-0.7 x 10(-8)mol/g tissue; Ka(2)=1.6 x 10(4)+/-0.9 x 10(4)l/mol, N(2)=1.7 x 10(-7)+/-0.4 x 10(-7)mol/g tissue). Chronic alcohol exposure had no effect on the degree of acetaldehyde binding.
Conclusion:
This previously unidentified source of variability may partially explain why some foetuses are adversely affected by prenatal alcohol exposure while others are not.