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Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Magnesium sulfate attenuates lipopolysaccharides-induced acute lung injury in mice
Wu Li1, Xiaoling Wu1, Jialin Yu1
1Department of Pathogenic Microbiology, Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Yinchuan; Department of Microbiology and Molecular Biology, College of Life Science, Ningxia University, Yinchuan, Ningxia, China.
Abstract:
Acute lung injury (ALI) is a common and severe respiratory disease with high morbidity and mortality. Although some progress has been made in the past years, the pathogenesis of ALI is still poorly understood and the therapeutic outcome has still not been significantly improved. It is well-recognized that magnesium sulfate (MgSO4) possesses potent anti-inflammation capacity. The present study was designed to investigate the protective effects of MgSO4 in lipopolysaccharides (LPSs)-induced ALI taken into account that excessive inflammatory response plays critical role in the development of ALI. In this study, Kunming mice were intravenously injected with LPS through tail vein to establish the ALI model and in parallel, A549 cells were used to establish cell model. The lung wet-to-dry weight ratio, malondialdehyde (MDA) levels in lung tissue, lung permeability index, hematoxylin and eosin staining, cytokines in the serum and bronchoalveolar lavage fluid (BALF), neutrophil counts in BALF, LPS-induced A549 cell apoptosis as well as apoptosis-inducing factor (AIF), and Poly(ADP-ribose) polymerase-1 (PARP-1) expression in both mice and A549 cells were detected. Our results demonstrated that MgSO4 significantly attenuated the LPS-induced ALI, oxidative stress (decreased MDA levels), and lung inflammatory response. Moreover, MgSO4 exerted protective effects by mitigating LPS-induced A549 cell apoptosis. Furthermore, MgSO4 decreased the AIF and PARP-1 expression both in vivo and in vitro. Our results, taken together, demonstrated that MgSO4 is a potential therapeutic agent for ALI taken into consideration that MgSO4 is commonly used in clinical settings.
Insights
Magnesium sulfate (MgSO4) effectively treats acute lung injury (ALI) by reducing inflammation and oxidative stress. This study shows MgSO4 protects against lipopolysaccharide-induced ALI in mice and cells, offering a potential therapeutic strategy.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Cell Biology
Background:
- Acute lung injury (ALI) presents significant morbidity and mortality with incompletely understood pathogenesis.
- Current therapeutic outcomes for ALI remain suboptimal, necessitating novel treatment strategies.
- Magnesium sulfate (MgSO4) is recognized for its anti-inflammatory properties, suggesting potential in ALI management.
Purpose of the Study:
- To investigate the protective effects of magnesium sulfate (MgSO4) against lipopolysaccharide (LPS)-induced acute lung injury (ALI).
- To elucidate the mechanisms underlying MgSO4's therapeutic potential in ALI, focusing on inflammation and apoptosis.
Main Methods:
- Establishment of LPS-induced ALI models in Kunming mice and A549 cells.
- Assessment of lung injury markers including wet-to-dry weight ratio, malondialdehyde (MDA) levels, and lung permeability.
- Evaluation of inflammatory cytokines, neutrophil counts, and apoptosis-related factors (AIF, PARP-1) in vivo and in vitro.
Main Results:
- Magnesium sulfate (MgSO4) significantly attenuated LPS-induced ALI, reducing lung injury and oxidative stress (decreased MDA levels).
- MgSO4 mitigated the inflammatory response, evidenced by reduced cytokines and neutrophil infiltration in bronchoalveolar lavage fluid (BALF).
- MgSO4 inhibited LPS-induced apoptosis in A549 cells by decreasing apoptosis-inducing factor (AIF) and Poly(ADP-ribose) polymerase-1 (PARP-1) expression.
Conclusions:
- Magnesium sulfate (MgSO4) demonstrates significant protective effects against acute lung injury (ALI) in both animal and cellular models.
- The therapeutic benefits of MgSO4 in ALI are attributed to its anti-inflammatory and anti-apoptotic properties, involving modulation of AIF and PARP-1.
- Given its established clinical use, MgSO4 represents a promising therapeutic agent for managing acute lung injury (ALI).

