Related Experiment Video
Updated: Jun 1, 2026
Non-Invasive Endotracheal Administration of Lipopolysaccharide to Induce Acute Lung Injury in Rodents
Published on: December 5, 2025
Magnesium sulfate mitigates acute lung injury in endotoxemia rats
Chun-Yi Lee1, Woan-Ching Jan, Pei-Shan Tsai
1Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, and Department of Nursing, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
Background:
Magnesium sulfate (MgSO4) possesses potent anti-inflammation capacity. We sought to elucidate the effects of MgSO4 on mitigating acute lung injury induced by endotoxemia. MgSO4 is an antagonist of the L-type calcium channels and the N-methyl-D-aspartate (NMDA) receptor. The roles of the L-type calcium channels and NMDA receptor in this regard were also elucidated.
Methods:
Ninety-six adult male rats were randomized to receive normal saline, MgSO4 (100 mg/kg), lipopolysaccharide (LPS), LPS plus MgSO4 (10, 50, or 100 mg/kg), LPS plus MgSO4 (100 mg/kg) plus the L-type calcium channel activator BAY-K8644, or LPS plus MgSO4 (100 mg/kg) plus exogenous NMDA (n=12 in each group). Between-group differences in lung injury were evaluated.
Results:
Histologic findings, in concert with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that LPS induced acute lung injury. LPS also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E2 concentrations) and imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations) in rat lungs. MgSO4 at the dosages of 50 mg/kg and 100 mg/kg, but not at 10 mg/kg, significantly mitigated the acute lung injury, lung inflammatory response, and oxidative stress caused by endotoxemia. Moreover, the protective effects of MgSO4 were counteracted by BAY-K8644 and exogenous NMDA.
Conclusions:
MgSO4 mitigates lung inflammatory response, oxidative stress, and acute lung injury in endotoxemia rats in a dose-dependent manner. The mechanisms may involve antagonizing the L-type calcium channels and the NMDA receptor.
Insights
Magnesium sulfate (MgSO4) effectively reduces inflammation and acute lung injury in endotoxemia models. Its protective effects are dose-dependent and may involve blocking calcium channels and NMDA receptors.
Area of Science:
- Pharmacology
- Pulmonology
- Toxicology
Background:
- Magnesium sulfate (MgSO4) exhibits anti-inflammatory properties.
- Acute lung injury (ALI) induced by endotoxemia is a significant clinical concern.
- MgSO4 acts as an antagonist for L-type calcium channels and N-methyl-D-aspartate (NMDA) receptors.
Purpose of the Study:
- To investigate the efficacy of MgSO4 in mitigating endotoxemia-induced ALI in rats.
- To elucidate the role of L-type calcium channels and NMDA receptors in MgSO4's protective effects against ALI.
Main Methods:
- Ninety-six male rats were divided into groups receiving saline, lipopolysaccharide (LPS), or LPS with varying doses of MgSO4.
- Additional groups received MgSO4 with L-type calcium channel activator (BAY-K8644) or exogenous NMDA.
- Lung injury was assessed via histology, leukocyte infiltration, lung water content, and biochemical markers of inflammation and oxidative stress.
Main Results:
- LPS induced significant acute lung injury, inflammation, and oxidative stress.
- MgSO4 (50 and 100 mg/kg) significantly attenuated LPS-induced lung injury, inflammation, and oxidative stress in a dose-dependent manner.
- The protective effects of MgSO4 were reversed by BAY-K8644 and exogenous NMDA administration.
Conclusions:
- Magnesium sulfate demonstrates a dose-dependent protective effect against acute lung injury, inflammation, and oxidative stress in endotoxemia.
- The therapeutic mechanisms of MgSO4 likely involve the antagonism of L-type calcium channels and NMDA receptors.
