400 DOES DRUG ADDICTION DUPING PREGNANCY ZNHANCE DRUG BIOTRANSFORMATION BY THE PLACENTA?

Abstract

The placenta is not merely a passive barrier to drugs and foreign chemicals, but may participate in xenobiotic biotransformation, as well. It is not known whether chronic addiction during pregnancy enhances this placental function. We therefore studied placental homogenates from 5 normal control and 7 drug dependent mothers and compared their oxidoreductase and transferase activities (μmoles/mg protein/h). RESULTS: (1) Reductase activity (measured by neoprontosil reduction) was higher in the soluble than microsomal fractions, due mostly to catalysis by NADPH. No significant difference was seen in the reductase activity of control (0.72 ± 0.06) vs addict (0.74 ± 0.16) in the supernate. (2) Transferee activity (by bilirubin conjugation) was minimal in both soluble and microsomal fractions. No significant difference was noted in the microsomal transferase activity of control (0.11 ± 0.06) vs addict (0.12 ± 0.05) homogenates. (3) Mixed function oxidoreductase activity (by aniline p-hydroxylation) appeared higher in the soluble (0.64 ± 0.24) than the microsomal (0.21 ± 0.14) fractions but due solely to hemoglobin in the soluble fraction which nonenzymatically catalyses aniline hydroxylation (49.4 × 10−4umoles/mg Hgb). No enzymatic oxidoreductase activity was noted in the control or addict homogenates. CONCLUSION: Little to no xenobiotic oxidoreductase and transferase activity was noted in both control and addict placental homogenates. Apparent activity was principally due to nonenzymatic catalysis of substrates by NADPH or Hgb. Thus, despite chronic exposure to drugs, the placenta of drug addicted mothers does not show any enhanced xenobiotic biotransformation activity and therefore offers no adaptive protection to the fetus.