METFORMIN’S IMPACT ON SERUM IMUNOGLOBULINS AND BRONCHOALVEOLAR LAVAGE CELLS IN MICE WITH COMPLICATED SEVERE ASTHMA
DOI:
https://doi.org/10.22551/MSJ.2024.02.13Abstract
Background: Severe asthma represents an important burden of mortality and morbidity in asthma being a clinical condition that has the risk of evolution to acute lung injury (ALI). Based on the anti-inflammatory and airway anti-remodeling effect of Metformin we presumed that it will promote beneficial effects in severe asthma complicated to ALI. Our study aimed to evaluate the effects of Metformin on a murine model of severe asthma complicated with ALI by assessing the modulatory effect of Metformin of plasma IgE levels and on differential cell count from bronchoalveolar lavage fluid. Materials and methods: There were three groups of BALB/c mice with ovalbumin (OVA)-induced asthma followed by ALI induction which consisted in OVA sensitization (days 0 and 7) and challenge (days 14, 15, 16 and 17) followed by lipopolysaccharide (LPS) intratracheal instillations (days 15 and 17) treated 30 min before OVA, in days 14-17: positive control group for disease (OVA+LPS), Dexamethasone treatment group (DEXA + OVA + LPS) and Metformin treatment group (OVA + LPS + METF). Measurement of OVA-specific IgE levels was made and bronchoalveolar lavage fluid (BALF) was collected in order to apply differential cell count. Results: administration of Metformin decreased the airway macrophage infiltration with no modulatory effect on airway neutrophilic infiltration. Conclusions: Metformin has the potential to influence the physio-pathological changes that occur in asthma followed by ALI. However, new studies to explore the specific mechanism by which Metformin influences the inflammatory and immune response in asthma/ALI overlap are needed.
References
2. Al Heialy S, Ramakrishnan RK, Hamid Q. Recent advances in the immunopathogenesis of severe asthma. J Allergy Clin Immunol 2022; 149(2): 455-465.
3. Zaidi SR, Blakey JD. Why are people with asthma susceptible to pneumonia? A review of factors related to upper airway bacteria. Respirol 2019; 24(5): 423-430.
4. Long ME, Mallampalli RK, Horowitz JC. Pathogenesis of pneumonia and acute lung injury. Clin Sci (Lond) 2022; 136(10): 747-769.
5. Wang Y, Wang Y, Ma J, et al. Yu Ping Feng San ameliorates LPS-induced acute lung injury and gut barrier dysfunction in mice. J Ethnopharmacol 2023; 312: 116452.
6. He YQ, Zhou CC, Yu LY, et al. Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms. Pharmacol Res 2021; 163: 105224.
7. LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocr Rev 2021; 42(1): 77-96.
8. Flory J, Lipska K. Metformin in 2019. JAMA 2019; 321(19): 1926-1927.
9. Park CS, Bang BR, Kwon HS, et al. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochem Pharmacol 2012; 84(12): 1660-1670.
10. Medeiros ML, Oliveira AL, Mello GC, Antunes E. Metformin Counteracts the Deleterious Effects of Methylglyoxal on Ovalbumin-Induced Airway Eosinophilic Inflammation and Remodeling. Int J Mol Sci 2023; 24(11): 9549 / doi: 10.3390/ ijms 24119549.
11. Bharath LP, Nikolajczyk BS. The intersection of Metformin and inflammation. Am J Physiol Cell Physiol 2021; 320(5): C873-C879.
12. Debeuf N, Haspeslagh E, Van Helden M, Hammad H, Lambrecht BN. Mouse Models of Asthma. CP Mouse Biology 2016; 6(2): 169-184.
13. Ehrentraut H, Weisheit CK, Frede S, Hilbert T. Inducing Acute Lung Injury in Mice by Direct In-tratracheal Lipopolysaccharide Instillation. J Vis Exp JOVE2019; (149) / doi: 10.3791/59999.
14. Medeiros ML, Oliveira AL, de Oliveira MG, Mónica FZ, Antunes E. Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin. J Inflamm Res 2021; 14: 6477-6489.
15. Yu LL, Zhu M, Huang Y, et al. Metformin relieves acute respiratory distress syndrome by reducing miR-138 expression. Eur Rev Med Pharmacol Sci 2018; 22(16): 5355-5363.
16. Zhang Y, Zhang H, Li S, Huang K, Jiang L, Wang Y. Metformin Alleviates LPS-Induced Acute Lung Injury by Regulating the SIRT1/NF-κB/NLRP3 Pathway and Inhibiting Endothelial Cell Pyroptosis. Front Pharmacol 2022; 13: 801337.
17. Aggarwal NR, King LS, D’Alessio FR. Diverse macrophage populations mediate acute lung inflam-mation and resolution. Am J Physiol Lung Cell Mol Physiol 2014; 306: L709-L725.
18. Lee JW, Chun W, Lee HJ, et al. The Role of Macrophages in the Development of Acute and Chronic Inflammatory Lung Diseases. Cells 2021; 10(4): 897 / doi: 10.3390/cells 10040897.
19. Chen X, Tang J, Shuai W, Meng J, Feng J, Han Z. Macrophage polarization and its role in the patho-genesis of acute lung injury/acute respiratory distress syndrome. Inflamm Res. 2020; 69(9): 883-895.
20. Wang M, Gao P,Wu X, et al. Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma. Respir Res. 2016; 17(1): 153.
21. Lee Y-M, Kang N-I, Lee H-K. Dexamethasone Does Not Inhibit Airway CXC Chemokine Expression and Neutrophilia in a Murine Model of Asthma: Mechanism of Steroid Resistance in Asthma. Immune Network 2007; 7(1): 18-25.
22. Wu TD, Keet CA, Fawzy A, Segal JB, Brigham EP, McCormack MC. Association of Metformin Initiation and Risk of Asthma Ex-acerbation. A Claims-based Cohort Study. Ann Am Thorac Soc 2019; 16(12): 1527-1533.
23. Yen FS, Hsu CC, Shih YH, Pan WL, Wei JC, Hwu CM. Metformin and the Development of Asthma in Patients with Type 2 Diabetes. Int J Environ Res Public Health 2022; 19(13): 8211.
Additional Files
Published
Issue
Section
License
COPYRIGHT
Once an article is accepted for publication, MSJ requests a transfer of copyrights for published articles.
COPYRIGHT TRANSFER FORM FOR
REVISTA MEDICO-CHIRURGICALĂ A SOCIETĂȚII DE MEDICI ȘI NATURALIȘTI DIN IAȘI /
THE MEDICAL-SURGICAL JOURNAL OF THE SOCIETY OF PHYSICIANS AND NATURALISTS FROM IASI
We, the undersigned authors of the manuscript entitled
_____________________________________________________________________________________
_____________________________________________________________________________________
warrant that this manuscript, which is submitted for publication in the REVISTA MEDICO-CHIRURGICALĂ, has not been published and it is not under consideration for publication in another journal.
- we give the consent for publication in the REVISTA MEDICO-CHIRURGICALĂ, in printed and electronic format and we transfer unconditioned and complete the copyright of this manuscript to the REVISTA MEDICO-CHIRURGICALĂ, in the event of its acceptance.
- the manuscript does not break the intellectual property rights of any other person.
- we have read the submitted version of the manuscript and we are fully responsible for the content.
Names and signatures of authors / copyright owners (the following sequence is the authorship of the article):
- ______________________________/_________________________
- ______________________________/_________________________
- ______________________________/_________________________
N.B. All the authors must sign this form