title: A synthetic analog of lipoxin A4 partially alleviates dexamethasone-induced fetal growth restriction in rats.
abstract: Fetal growth restriction (FGR) is a major cause of neonatal morbidity and mortality. There is evidence to show that FGR is associated with oxidative stress. Lipoxin A4 (LXA4) is an anti-inflammatory mediator and is considered to be a potent endogenous "stop signal" in inflammation. LXA4 has been extensively studied preclinically in many diseases related to inflammation. Recently, the antioxidant effect of LXA4 on a variety of cell types has been reported. In the current study, we tested the effect of LXA4 on rats with experimental FGR. Dexamethasone (DEX) was administered to pregnant rats in order to induce FGR and BML-111, a synthetic analog of LXA4, was administrated as antioxidant therapy. DEX caused increased oxidative stress and trophoblast cell apoptosis in the placenta, leading to decreased placental weight and fetal weight at term. These effects were partially alleviated by BML-111. As a possible mechanism for this improvement in weight, BML-111 was found to promote nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), up-regulate the expression of antioxidant enzyme genes, superoxide dismutase (SOD) and glutathione peroxidase (GPx), and consequently inhibited trophoblast cells apoptosis. This study demonstrates for the first time that LXA4 could potentially alleviate FGR in DEX-exposed pregnant rats.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: F
authors.initials: F
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: P
authors.initials: P
authors.lastname: Zeng
authors.forename: D
authors.initials: D
authors.lastname: Ye
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003907:Dexamethasone; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000517:prevention & control*; D005979:Glutathione Peroxidase; D006538:Heptanoic Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D044045:Lipoxins; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D013482:Superoxide Dismutase; D014327:Trophoblasts / Q000166:cytology
chemical_list: C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D000975:Antioxidants; D006538:Heptanoic Acids; D044045:Lipoxins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C040527:lipoxin A4; D003907:Dexamethasone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Apoptosis; Fetal growth restriction; Lipoxin; Oxidative stress; Trophoblast