ArticlePediatric research2023
L-citrulline attenuates lipopolysaccharide-induced inflammatory lung injury in neonatal rats.
Article in Pediatric research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Bronchopulmonary Dysplasia and Innate Immunity: A Narrative Review of the Roles of IL-1β and IL-8 (CXCL8).Children (Basel, Switzerland) · 2026Review
- L-Citrulline in Maternal-Fetal and Neonatal Health: Metabolic Mechanisms and Emerging Therapeutic Applications.Nutrients · 2026Review
- L-Citrulline: Novel Pharmacotherapy to Improve Outcomes in Infants and Children at Risk of Systemic or Pulmonary Vascular Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mitochondrial quality control mechanisms as molecular targets for impaired lung development: from fetuses to neonates.Respiratory research · 2025Review
- Gut Microbiota and Its Metabolites Modulate Pregnancy Outcomes by Regulating Placental Autophagy and Ferroptosis.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- Jiawei Buyang Huanwu Decoction modulates gut microbiota and metabolic profiles in a rat model of idiopathic pulmonary fibrosis.Frontiers in microbiology · 2025Article
- Heliox preconditioning exerts pulmonary protection effects on neonatal acute respiratory distress syndrome by inhibiting oxidative stress and apoptosis.Frontiers in pharmacology · 2025Article
- Safety, Efficacy and Bio-Distribution Analysis of Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells for Effective Treatment of Bronchopulmonary Dysplasia by Intranasal Administration in Mice Model.International journal of nanomedicine · 2025Article
- L-Citrulline in Neonates: From Bench to Bed Side.Children (Basel, Switzerland) · 2024Review
- Metabolic reprogramming in sepsis-associated acute kidney injury: insights from lipopolysaccharide-induced oxidative stress and amino acid dysregulation.Molecular biology reports · 2024Article
- Linoleic Acid Promotes Mitochondrial Biogenesis and Alleviates Acute Lung Injury.The clinical respiratory journal · 2024Article
- Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients.International journal of molecular sciences · 2024Article
- Analysis of blood metabolite characteristics at birth in preterm infants with bronchopulmonary dysplasia: an observational cohort study.Frontiers in pediatrics · 2024Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrenatal or postnatal lung inflammation and oxidative stress disrupt alveolo-vascular development leading to bronchopulmonary dysplasia (BPD) with and without pulmonary hypertension. L-citrulline (L-CIT), a nonessential amino acid, alleviates inflammatory and hyperoxic lung injury in preclinical models of BPD. L-CIT modulates signaling pathways mediating inflammation, oxidative stress, and mitochondrial biogenesis-processes operative in the development of BPD. We hypothesize that L-CIT will attenuate lipopolysaccharide (LPS)-induced inflammation and oxidative stress in our rat model of neonatal lung injury.
methodsNewborn rats during the saccular stage of lung development were used to investigate the effect of L-CIT on LPS-induced lung histopathology and pathways involved in inflammatory, antioxidative processes, and mitochondrial biogenesis in lungs in vivo, and in primary culture of pulmonary artery smooth muscle cells, in vitro.
resultsL-CIT protected the newborn rat lung from LPS-induced: lung histopathology, ROS production, NFκB nuclear translocation, and upregulation of gene and protein expression of inflammatory cytokines (IL-1β, IL-8, MCP-1α, and TNF-α). L-CIT maintained mitochondrial morphology, increased protein levels of PGC-1α, NRF1, and TFAM (transcription factors involved in mitochondrial biogenesis), and induced SIRT1, SIRT3, and superoxide dismutases protein expression.
conclusionL-CIT may be efficacious in decreasing early lung inflammation and oxidative stress mitigating progression to BPD. IMPACT: The nonessential amino acid L-citrulline (L-CIT) mitigated lipopolysaccharide (LPS)-induced lung injury in the early stage of lung development in the newborn rat. This is the first study describing the effect of L-CIT on the signaling pathways operative in bronchopulmonary dysplasia (BPD) in a preclinical inflammatory model of newborn lung injury. If our findings translate to premature infants, L-CIT could decrease inflammation, oxidative stress and preserve mitochondrial health in the lung of premature infants at risk for BPD.
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