Related Experiment Video
Updated: Nov 12, 2025
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in
Dan Chen1, Zhi-Qi Gao1, Ying-Ying Wang1
1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China.
Insights
Sodium propionate (SP) mitigates lung damage in bronchopulmonary dysplasia (BPD) by reducing inflammation and oxidative stress. This protection is mediated through the Nrf2 pathway, improving alveolar structure and blood vessel growth.
Area of Science:
- Pulmonary Medicine
- Neonatal Research
- Molecular Biology
Background:
- Bronchopulmonary dysplasia (BPD) is characterized by alveolar arrest and impaired angiogenesis, driven by chronic inflammation and oxidative stress.
- Short-chain fatty acids (SCFAs), particularly propionate, exhibit anti-inflammatory and antioxidant properties.
- Investigating sodium propionate's (SP) therapeutic potential in a lipopolysaccharide (LPS)-induced BPD model is crucial.
Purpose of the Study:
- To evaluate the protective effects of sodium propionate (SP) against LPS-induced bronchopulmonary dysplasia (BPD) in a neonatal mouse model.
- To elucidate the underlying mechanisms of SP's action, focusing on the Nrf2 signaling pathway.
- To assess SP's impact on pulmonary inflammation, oxidative stress, alveolar structure, and angiogenesis.
Main Methods:
- Utilized wild-type (WT) and Nrf2-deficient (Nrf2-/-) mice, along with human pulmonary microvascular endothelial cells (HPMECs).
- Induced BPD models in vivo and in vitro using lipopolysaccharide (LPS).
- Assessed lung histopathology, inflammation, oxidative stress markers, cell viability, and angiogenesis.
Main Results:
- SP treatment increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) in LPS-induced BPD mice.
- SP reduced pulmonary inflammation and oxidative stress, improving alveolar pathology in WT but not Nrf2-/- mice.
- In LPS-challenged HPMECs, SP promoted Nrf2 nuclear translocation, enhanced cell viability, supported angiogenesis, and inhibited the NF-κB pathway. Nrf2 inhibition (ML385) abolished SP's benefits.
Conclusions:
- Sodium propionate (SP) demonstrates significant protective effects against lung alveolar simplification and abnormal angiogenesis in LPS-induced BPD.
- These beneficial effects are dependent on the Nrf2 signaling pathway.
- SP holds promise as a therapeutic agent for BPD, targeting inflammation and oxidative stress via Nrf2 activation.
Background:
Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.
Methods:
WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.
Results:
The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.
Conclusion:
SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.
