Related Experiment Video
Updated: May 29, 2025
Intratracheal Instillation of Stem Cells in Term Neonatal Rats
Published on: May 4, 2020
Celastrol has beneficial effects on pulmonary hypertension associated with bronchopulmonary dysplasia: Preclinical
Claire-Marie Pilard1, Guillaume Cardouat2, Isabel Gauthereau2
1Plateforme Technologique d'Innovation Biomédicale, Pessac F-33600, France; INSERM U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, University of Bordeaux, Pessac F-33600, France; Neonatology Department, Bordeaux University Hospital, Bordeaux F-33000, France.
Insights
Celastrol, an anti-inflammatory and antioxidant molecule, prevented mortality in a neonatal rat model of bronchopulmonary dysplasia with pulmonary hypertension (BPD-PH). It reduced key disease markers, suggesting potential as a BPD-PH treatment.
Area of Science:
- Neonatal cardiorespiratory disease
- Pulmonary hypertension research
- Pharmacological interventions
Background:
- Bronchopulmonary dysplasia with pulmonary hypertension (BPD-PH) is a severe neonatal condition with high mortality and no cure.
- Inflammation and oxidative stress are key pathological pathways in BPD-PH.
- Celastrol, a natural molecule, exhibits anti-inflammatory and antioxidant properties.
Purpose of the Study:
- To evaluate celastrol as a potential preventive treatment for BPD-PH.
- To investigate the effects of celastrol on hyperoxia-induced pulmonary hypertension in a neonatal rat model.
- To explore the molecular mechanisms of celastrol in human fetal pulmonary artery smooth muscle cells.
Main Methods:
- Neonatal rats were exposed to hyperoxia to model BPD-PH, with some receiving celastrol treatment.
- In vivo assessments included mortality, pulmonary hypertension, right ventricular hypertrophy, vascular remodeling, and inflammation markers.
- In vitro studies used human fetal pulmonary artery smooth muscle cells (HfPA-SMC) exposed to hyperoxia to assess celastrol's effects on calcium signaling and inflammation.
Main Results:
- Celastrol treatment prevented mortality in the hyperoxia-exposed rat model.
- Celastrol reduced pulmonary hypertension, right ventricular hypertrophy, vascular remodeling, and inflammation.
- Celastrol inhibited endothelin-1-induced calcium response in HfPA-SMC and decreased pro-inflammatory cytokine secretion.
- Celastrol induced heme oxygenase-1 (HO-1) expression in both rat lungs and human cells.
Conclusions:
- Celastrol demonstrates a preventive effect against key features of BPD-PH in a neonatal rat model.
- Celastrol's protective mechanisms involve modulating macrophage inflammatory signaling and smooth muscle cell calcium cycling.
- Celastrol shows promise as a potential therapeutic agent for preventing BPD-PH.
Abstract:
Pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) is a severe cardiorespiratory disease of preterm newborns leading to an excess of mortality in infancy and no curative treatment currently exists. Inflammation and oxidative stress are the common pathways that lead to BPD-PH. Therefore, we aimed to evaluate celastrol, a molecule with anti-inflammatory and antioxidant properties, as a promising preventive treatment in BPD-PH. In a model of neonatal rats exposed to hyperoxia, we demonstrated that mortality was prevented in animals treated with celastrol. Moreover, in vivo, celastrol decreased pulmonary hypertension, right ventricular hypertrophy, vascular remodeling, pulmonary arterial hyperreactivity to endothelin-1 and inflammation but had no effect on hypoalveolarization and altered angiogenesis. In vitro experiments carried out on human fetal pulmonary artery smooth muscle cells (HfPA-SMC) exposed to hyperoxia showed that endothelin-1-induced intracellular calcium response was increased and celastrol significantly inhibited this effect, without modifying endothelin-1 receptors expression. Regarding inflammation, celastrol decreased both CD68 staining in lung and secretion of the pro-inflammatory cytokine Tissue Inhibitor of Metalloproteinases-1 in intrapulmonary arteries from neonatal rats. IL-6 secretion was also decreased by celastrol in HfPA-SMC. Finally, hyperoxia increased heme oxygenase-1 (HO-1) expression and celastrol induced an overexpression of HO-1 in both neonatal rat lung and human cells. These results suggest that celastrol has a preventive effect on major hallmarks of PH in both a rat hyperoxic model of BPD-PH and HfPA-SMC exposed to hyperoxia via modulation of macrophage inflammatory signaling and HfPA-SMC calcium cycling. Celastrol could therefore be considered as a promising preventive treatment in BPD-PH.
Related Concept Videos
01:24Antiasthma Drugs: Methylxanthines
Theophylline is thought to inhibit phosphodiesterase enzymes, increasing intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). This rise in cAMP and cGMP concentrations stimulates cardiac function,...
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:23Upper Respiratory Drugs: Antitussives, Expectorants, and Mucolytics
Antitussives include codeine, dextromethorphan (Robitussin), and benzonatate (Tessalon). Codeine and dextromethorphan exert their effects centrally by suppressing the cough reflex center in the medulla. Benzonatate operates peripherally within the respiratory tract by...
01:25Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:26COPD: Management Using Bronchodilators and Corticosteroids