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A synthetic analog of lipoxin A4 partially alleviates dexamethasone-induced fetal growth restriction in rats
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Insights
Lipoxin A4 (LXA4) shows potential in treating fetal growth restriction (FGR). This antioxidant therapy, using a synthetic LXA4 analog, reduced oxidative stress and apoptosis in a rat model of FGR.
Area of Science:
- Reproductive Biology
- Pharmacology
- Cell Biology
Background:
- Fetal growth restriction (FGR) significantly contributes to neonatal complications.
- Oxidative stress is implicated as a key factor in the pathophysiology of FGR.
- Lipoxin A4 (LXA4), an endogenous anti-inflammatory mediator, has demonstrated antioxidant properties.
Purpose of the Study:
- To investigate the therapeutic potential of LXA4 as an antioxidant therapy for experimental FGR.
- To evaluate the effects of a synthetic LXA4 analog, BML-111, on FGR induced by dexamethasone (DEX) in rats.
Main Methods:
- Experimental FGR was induced in pregnant rats using dexamethasone (DEX).
- BML-111, a synthetic LXA4 analog, was administered as antioxidant therapy.
- Placental and fetal weights, oxidative stress markers, trophoblast cell apoptosis, and Nrf2 pathway activation were assessed.
Main Results:
- DEX administration led to increased placental oxidative stress, trophoblast apoptosis, and reduced placental and fetal weights.
- BML-111 treatment partially alleviated these DEX-induced effects.
- BML-111 promoted Nrf2 nuclear translocation, up-regulated antioxidant enzymes (SOD, GPx), and inhibited trophoblast apoptosis.
Conclusions:
- Lipoxin A4 analog BML-111 demonstrates a protective effect against experimental fetal growth restriction.
- The antioxidant and anti-apoptotic mechanisms involving Nrf2 activation are key to LXA4's therapeutic potential in FGR.
- LXA4 represents a promising therapeutic avenue for managing FGR.
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.
