title: NAD(P)H oxidase associated superoxide production in human placenta from normotensive and pre-eclamptic women.
abstract: Oxidative stress plays an important role in the development of pre-eclampsia. Recently, the superoxide producing enzyme NAD(P)H oxidase was shown to be present in placental trophoblast. In this pilot-study we investigated the NAD(P)H oxidase associated superoxide production as modulator of placental oxidative stress in normotensive pregnancy (n = 19; gestational age 38(+6)+/-0(+1)weeks(+days)) and pre-eclampsia (n = 15; gestational age 34(+3)+/-1(+5)weeks(+days)) using a lucigenin assay. Specificity of superoxide generation by NAD(P)H oxidase was assessed using the inhibitors L-NAME, rotenone, allopurinol, DPI and TIRON. Superoxide production was measurable in all placenta tissues and was inhibited by DPI and TIRON. No significant differences for total superoxide production (O2*total), maximal superoxide production (O2*max), or the rate of superoxide production were found between normotensive and pre-eclamptic women. However, women with early onset of disease had a higher O2*total as compared to those with a late onset disease. We conclude that human placenta contains a functional NAD(P)H oxidase that is highly active, which could be an important source of superoxide during pregnancy and pre-eclampsia. These data justify more detailed investigation of the role of NAD(P)H oxidase and placental oxidative stress in complicated pregnancies.
authors.affiliation: Maternal and Fetal Research Unit, GKT School of Medicine, St Thomas' Hospital, London SE1 7EH, UK. maarten.raijmarkers@kcl.ac.uk
authors.forename: M T M
authors.initials: MT
authors.lastname: Raijmakers
authors.forename: W H M
authors.initials: WH
authors.lastname: Peters
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: L
authors.initials: L
authors.lastname: Poston
mesh_terms: D000328:Adult; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006801:Humans; D006973:Hypertension; D066298:In Vitro Techniques; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019255:NADPH Oxidases; D018384:Oxidative Stress; D011225:Pre-Eclampsia / Q000201:enzymology* / Q000503:physiopathology; D011247:Pregnancy; D013481:Superoxides / Q000378:metabolism*; D014327:Trophoblasts / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases