Purpose: Acute respiratory distress syndrome (ARDS), a severe medical condition, is among the major causes of death in critically ill patients. Morphine is used as a therapeutic agent against severe pain. The mechanisms of its reactions over ARDS are not fully understood. The aim of this study was to assess the mechanism of morphine in rats with ARDS.
Methods: Rats were injected with lipopolysaccharide to induce ARDS, and some rats were pre-treated with graded doses of morphine in the lateral ventricles to assess survival and non-infected mortality. Immunohistochemical and HE staining were performed to measure MPO and CD68 activity in the lungs and lung injury. ELISA was conducted to detect the inflammatory factor levels in the plasma and BALF. Co-labeling of μ-opioid receptor (MOR) and c-Fos was observed in the brain tissues. MOR-positive cells in brain tissues were evaluated using immunohistochemistry. The effect of MOR antagonists on ARDS was examined in rats by pre-injection of naloxone or methylnaltrexone. The expression of MyD88, TLR4, and NF-κB was lastly assessed.
Results: Dose-independent improvement was observed in respiratory capacity and lung injury in ARDS rats after morphine pre-injection, along with reduced inflammatory factors in the plasma and BALF. MOR-positive cells were elevated after morphine, which occurred within the ventral part of the gigantocellular reticular nucleus (GiV). Naloxone and methylnaltrexone blocked the effects of morphine via central and peripheral MOR. Morphine activated TLR pathway in a MyD88-dependent manner.
Conclusion: Morphine activates MOR within the GiV and the TLR pathway to attenuate ARDS in rats.
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http://dx.doi.org/10.1016/j.yexcr.2022.113224 | DOI Listing |
BMC Pharmacol Toxicol
January 2025
Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
Background: In patients with sepsis, platelets are activated and adhere to neutrophils, forming platelet-leukocyte aggregates (PLAs) that lead to the development of MODS. ARDS is one of the main manifestations of septic MODS. We designed this study to explore the effects of different anti-plate therapy drugs on platelet activation and platelet-leukocyte aggregate (PLA) formation in the early stage of septic ARDS.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Dr. Babasaheb Ambedkar Technological University, Lonere, Raigad, 402103, India.
Acute lung injury i.e. ALI and its serious form acute respiratory distress syndrome (ARDS) are incurable medical conditions associated with significant global mortality and morbidity.
View Article and Find Full Text PDFmBio
December 2024
Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland, USA.
Influenza, as well as other respiratory viruses, can trigger local and systemic inflammation resulting in an overall "cytokine storm" that produces serious outcomes such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We hypothesized that gene therapy platforms could be useful in these cases if the production of an anti-inflammatory protein reflects the intensity and duration of the inflammatory condition. The recombinant protein would be produced and released only in the presence of the inciting stimulus, avoiding immunosuppression or other unwanted side effects that may occur when treating infectious diseases with anti-inflammatory drugs.
View Article and Find Full Text PDFInt J Artif Organs
December 2024
Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, China.
Background: The major concerns for patients who have acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 or sepsis and undergone successful venovenous extracorporeal membrane oxygenation (VV ECMO) include a low survival rate and an uncontrollable inflammatory response. This study aimed to introduce an inflammation-related ALI/ARDS rat model supported by VV ECMO that is more suitable for clinical application to assess the immune response and thereby further improve survival after VV ECMO.
Methods: Rats were randomly divided into three groups: the sham group, the lipopolysaccharide (LPS) group, and the LPS + ECMO group.
J Pharm Sci
January 2025
Department of Chinese Medicinal Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Yang Guang South Street, Fangshan District, Beijing 102488, China. Electronic address:
Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) with clinical manifestations of respiratory distress and hypoxemia remains a significant cause of respiratory failure, boasting a persistently high incidence and mortality rate. Given the central role of M1 macrophages in the pathogenesis of acute lung injury (ALI), this study utilized the anti-inflammatory agent curcumin as a model drug. l-arginine (L-Arg) was employed as a targeting ligand, and chitosan was initially modified with l-arginine.
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