Increased anti-oxidant enzyme activity and biological oxidation in placentae of pregnancies complicated by maternal asthma

Abstract

Our previous work has demonstrated that alterations in placental function are associated with changes in fetal development in pregnancies complicated by asthma. The pathophysiology of asthma in adults and children and intrauterine growth restriction during pregnancy are associated with oxidative stress. Based on this information, we examined whether placental anti-oxidant pathways and markers of biological oxidation were altered in pregnancies complicated by asthma. Anti-oxidant enzyme activities of superoxide dismutase, glutathione peroxidase and thioredoxin reductase, thioredoxin concentrations, lipid and protein oxidation levels were measured in placentae of pregnancies complicated by asthma and compared to uncomplicated, non-asthmatic pregnancies. Placental tissue homogenates of pregnancies complicated by asthma demonstrated significantly increased levels of lipid peroxidation (25.7+/-1.8 micromol/mg protein versus 12.1+/-1.6 micromol/mg protein, P=0.008) and protein carbonyl concentrations (414.6+/-51.4 units/mg protein versus 222.3+/-32.6 units/mg protein, P=0.0032) when compared to non-asthmatic controls. The activities of the anti-oxidant proteins superoxide dismutase (2.17+/-0.09 units/mg protein versus 1.67+/-0.09 units/mg protein, P=0.014) and thioredoxin reductase (54.0+/-6.9 units/mg protein versus 28.7+/-6.0 units/mg protein, P=0.009) were significantly increased in the presence of maternal asthma. Placental thioredoxin levels (102.9+/-5.3 ng/mg protein versus 92.9+/-8.6 ng/mg protein, P=0.37) and glutathione peroxidase activity (27.3+/-2.2 mmol/min/mg protein versus 28.3+/-2.2 mmol/min/mg, P=0.83) were not significantly different in pregnancies complicated by asthma and non-asthmatic pregnancies. There was no effect of fetal sex, asthma severity or treatment for asthma on these pathways. Maternal asthma during pregnancy is associated with increased placental enzymatic anti-oxidant capacity and also increased protein oxidation suggesting there is a compensatory increase in anti-oxidant activity in response to increased oxidative stress.