Effects of ethanol on alcohol dehydrogenase and microsomal ethanol oxidative system activities in fetal mice

In an attempt to better understand the mechanism of the fetal damage caused by ethanol, we studied the effects of its administration on the activity of some ethanol metabolizing enzymes in mice fetuses. Animals were given a single ethanol injection (0.01 ml of a 25% solution in 0.9% sodium chloride per gram of body weight) on day 12 of pregnancy and were divided into groups that were killed 24, 48, and 72 hours later. The fetal and maternal livers were isolated, homogenized, and divided into subcellular fractions. Alcohol dehydrogenase, NADH-cytochrome C reductase, NADPH-cytochrome C reductase, and cytochrome P-450 activities were measured and compared with those of control animals injected with saline solution. We found that ethanol caused (1) a significant but transient increase in fetal alcohol dehydrogenase activity, (2) a significant and persistent increase in fetal cytochrome P-450 and NADPH-cytochrome C reductase activities, and (3) no change in fetal NADH-cytochrome C reductase activity. These effects were similar although quantitatively smaller than those observed in the maternal liver and disappeared after pretreatment with metyrapone. This work demonstrates that ethanol has a similar effect upon both maternal and fetal ethanol metabolizing enzymes and gives experimental support to the possibility that a reactive product of the interaction between ethanol and the cytochrome P-450 system may be responsible for the embryotoxic effects of this compound.