Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response

Autor: Chen, Xueyu, Walther, Frans J, Sengers, Rozemarijn M A, Laghmani, El Houari, Salam, Asma, Folkerts, Gert, Pera, Tonio, Wagenaar, Gerry T M, Sub Airway in vivo Pharmacology, Pharmacology
Přispěvatelé: Sub Airway in vivo Pharmacology, Pharmacology
Rok vydání: 2015
Předmět:
Physiology
Drug Evaluation
Preclinical
Anti-Inflammatory Agents
Wistar
Gene Expression
Gastroenterology
Fibrosis
Medicine
Lung
Bronchopulmonary Dysplasia
Hyperoxia
Alveolar septum
respiratory system
Preclinical
Metformin
medicine.anatomical_structure
Call for Papers
Collagen
Drug
medicine.symptom
medicine.drug
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Lung injury
Capillary Permeability
Dose-Response Relationship
Right ventricular hypertrophy
Physiology (medical)
Internal medicine
Animals
Rats
Wistar
coagulation
Fibrin
Dose-Response Relationship
Drug
Hypertrophy
Right Ventricular
business.industry
lung inflammation
fibrosis
Hypertrophy
Cell Biology
Newborn
medicine.disease
Right Ventricular
Elastin
Rats
Endocrinology
Animals
Newborn
Bronchopulmonary dysplasia
Drug Evaluation
business
Zdroj: American journal of physiology. Lung cellular and molecular physiology, 309(3), L262. American Physiological Society
AJP-Lung Cellular and Molecular Physiology, 309(3), L262-L270
ISSN: 1522-1504
1040-0605
DOI: 10.1152/ajplung.00389.2014
Popis: Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic option for BPD by reducing pulmonary inflammation and fibrosis and improving vascularization. We investigated the therapeutic potential of daily treatment with 25 and 100 mg/kg metformin, injected subcutaneously in neonatal Wistar rats with severe experimental BPD, induced by continuous exposure to 100% oxygen for 10 days. Parameters investigated included survival, lung and heart histopathology, pulmonary fibrin and collagen deposition, vascular leakage, right ventricular hypertrophy, and differential mRNA expression in the lungs of key genes involved in BPD pathogenesis, including inflammation, coagulation, and alveolar development. After daily metformin treatment rat pups with experimental BPD had reduced mortality, alveolar septum thickness, lung inflammation, and fibrosis, demonstrated by a reduced influx of macrophages and neutrophils and hyperoxia-induced collagen III and fibrin deposition (25 mg/kg), as well as improved vascularization (100 mg/kg) compared with control treatment. However, metformin did not ameliorate alveolar enlargement, small arteriole wall thickening, vascular alveolar leakage, and right ventricular hypertrophy. In conclusion metformin prolongs survival and attenuates pulmonary injury by reducing pulmonary inflammation, coagulation, and fibrosis but does not affect alveolar development or prevent pulmonary arterial hypertension and right ventricular hypertrophy in neonatal rats with severe hyperoxia-induced experimental BPD.
Databáze: OpenAIRE
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