Influence of tobacco smoke constituents on monoamine oxidase activity in vitro and on human placental monoamine oxidase A activity in vivo
Sørensen, Izel Fourie
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The aim of this study was to investigate the influence of tobacco smoke on monoamine oxidase activity, and of smoking during pregnancy on placental monoamine oxidase A (MAO-A) activity. The enzyme MA0 exists in two isoforms, MAO-A and MAO-B, both of which are important in regulating monoamine status in the brain and periphery. Some substrate selectivity for particular monoamines is a characteristic of these isoforms, and one form of the enzyme may predominate in particular organs. Recreational tobacco smoking influences the status of monoamine oxidases in the body. In vivo studies using PET imaging have shown that both MAO-A and MAO-B activity are inhibited in the brains of smokers compared to non-smokers. In support of these findings are data that suggest that MAO-B catalytic activity is attenuated in blood platelets of smokers. Hitherto, no studies have assessed the influence of cigarette smoke on placental MA0 activity. Mammalian placenta is rich in MAO-A and activity of this isoform of the enzyme is found virtually exclusively in this organ. The activity of MAO-A in the placenta is of interest since it is thought to play a major role in regulating serotonin (a monoamine neurotransmitter and highly selective MAO-A substrate) within the placenta. Serotonin plays a very important role in the development of the fetus and it is evident that any xenobiotically-induced influence on the status of placental serotonin, including alteration of the activity of its metabolizing enzyme (i.e. MAO-A), should be of concern in pregnancy. A series of studies aimed at assessing the influence of tobacco smoke condensate and tobacco leaf extract on monoamine oxidase activity in general, has been performed. These included studies comparing the MA0 inhibitory effects of tobacco leaf extracts compared to the (whole/total/crude) cigarette smoke condensate, and studies to determine whether this inhibition is reversible. Studies that focused on MAO-A included the determination of the activity of this enzyme isolated from healthy placentas and the study of the influence of cigarette smoke condensate on placental mitochondrial MAO-A activity in vitro. These studies showed that cigarette smoke condensate is much more potent in inhibiting MA0 compared to tobacco leaf extracts. A very surprising finding was that smoke extracts of cigarettes that do not contain tobacco (Magic@ brand cigarettes) showed similar potencies for inhibiting MA0 than did smoke extracts of tobacco-containing cigarettes. It is dear that there is an irreversible component in the inhibition of MA0 by cigarette smoke condensate (in the A as well as the B form). The series of in vitro and ex vivo settings confirmed that tobacco smoke has a profound influence on MA0 activity by inhibiting the enzyme irreversibly. In order to determine the effects of maternal smoking during pregnancy specifically on MAO-A activity in the placenta, term placentas from smoking and non-smoking mothers were collected and the MAO-A activity measured in each case. Furthermore, the influence of MAO-A activity on serotonin levels was investigated by measuring serotonin levels in the umbilical cord blood and maternal blood associated with each placenta. It was hypothesized that a decrease in placental MAO-A activity should result in an increase in umbilical cord and maternal blood serotonin levels in placentas obtained from mothers who smoked during pregnancy. Our results showed slightly lower MAO-A activity in term placentas of smokers compared to non smokers. However, this influence was not significant Platelet MAO-B activity was found to be significantly lower (p < 0.1) in maternal platelet rich plasma (PRP) of smokers compared to non smokers. Determinations in maternal PRP revealed that serotonin concentrations expressed per volume is not different between smokers and non smokers. However, when the maternal serotonin concentrations are expressed per platelet, non smokers have significantly more @ < 0.05) serotonin present per platelet than smokers. From the literature there seems to be an inverse relationship between mean platelet volume and serotonin content which would argue that smokers in our study had smaller mean platelet volumes than non-smokers. We speculate that there is a compensatory mechanism responsible for the subsequently higher maternal platelet count (p < 0.05) in the smokers compared to the non smokers. Determinations in cord blood PRP showed no significant differences between smokers and non smokers with regards to serotonin levels, platelet counts and MAO-B activity. From these studies it can be concluded that extracts of tobacco leaves are less potent in inhibiting MA0 than extracts of cigarette smoke, leading one to speculate that pyrolysis products are mostly implicated in MA0 inhibition. Cigarette smoke extracts are more potent in inhibiting MAO-B than MAO-A in vitro. Despite the significant inhibition of MAO-A in vitro by extracts of cigarette smoke, placental MAO-A activity is not significantly inhibited by maternal smoking during pregnancy in vivo compared to women who do not smoke. However, platelet MAO-B activity was significantly inhibited in the smoker group compared to the non smoker group. These results leads one to speculate that the in vivo activity of placental MAO-A is somehow more "protected" against the effects of cigarette smoking than when this enzyme is tested in an in vitro environment.
- Health Sciences