Efficacy of phentolamine combined with ambroxol aerosol inhalation in the treatment of pediatric severe pneumonia and its effect on serum IL-10 and CRP levels

Li, Junxia; Wu, Haixia; Zhang, Jingyao

doi:10.21037/tp-21-516

Cited by 4 publications

(3 citation statements)

References 26 publications

(23 reference statements)

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“…Similarly, the results of Han et al [17] demonstrated that phentolamine significantly prevents acute kidney injury and reduces inflammation and apoptosis in mice. Previous studies have shown that phentolamine can significantly improve the inflammatory response and lung function in severe neonatal pneumonia [18]. This is the first time we have reported the inhibitory role of phentolamine on inflammation and apoptosis in embryonic lung cells.…”

Section: Discussionsupporting

confidence: 55%

Phentolamine Protects against Apoptosis and Inflammation in a Neonatal Pneumonia Cell Model Induced by LPS by Regulating the TrkA/Akt Signaling Pathways

Liu,

Wu,

Chen

et al. 2024

Discovery Medicine

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Background: Phentolamine is an α-adrenergic receptor blocker that can be used to treat neonatal pneumonia, but its underlying mechanism is unclear. The purpose of this study is to probe the function of phentolamine on lipopolysaccharide (LPS)-induced inflammation and cell death in an in vitro model of neonatal pneumonia. Methods: Human MRC-5 cells were incubated with varying doses of phentolamine in vitro to evaluate cell viability. Subsequently, LPS was introduced to further investigate the combined effects of phentolamine and LPS on cell viability and apoptosis in MRC-5 cells. The effect of phentolamine/LPS treatment on the Neurotrophic Tyrosine Kinase Receptor A (TrkA)/Protein Kinase B (Akt) signaling pathway and the phosphorylation of pathway proteins in MRC-5 cells was further analyzed via western blot. Additionally, knockout of TrkA and Akt genes in MRC-5 cells was performed to explore the effects of phentolamine/LPS treatment on cell viability, apoptosis levels, and inflammatory factor levels in MRC-5 cells. Results: Preincubation of MRC-5 cells with a low concentration of phentolamine (≤6 µg/mL) protected against LPS-induced cell inflammatory injury. Phentolamine promoted both TrkA and Akt phosphorylation and Akt activation induced by LPS in MRC-5 cells. The protective effect of phentolamine against LPS-induced apoptosis and inflammation was significantly reduced in response to TrkA or Akt gene knockdown in MRC-5 cells. Conclusions: Phentolamine may protect LPS-induced apoptosis and inflammation by activating the TrkA and Akt signaling pathways.

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Section: Discussionsupporting

confidence: 55%

Phentolamine Protects against Apoptosis and Inflammation in a Neonatal Pneumonia Cell Model Induced by LPS by Regulating the TrkA/Akt Signaling Pathways

Liu,

Wu,

Chen

et al. 2024

Discovery Medicine

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“…These factors have limited its widespread use [ 30 , 31 ]. Phentolamine has been widely used in clinical practice, and a large number of studies and clinical data have confirmed its safety [ 32 ]. The current study is the first to describe its use as an antibacterial agent.…”

Section: Discussionmentioning

confidence: 99%

Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Cui

Zheng

et al. 2023

Antibiotics

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Objectives: Multidrug-resistant (MDR) Gram-negative bacterial infections have limited treatment options due to the impermeability of the outer membrane. New therapeutic strategies or agents are urgently needed, and combination therapies using existing antibiotics are a potentially effective means to treat these infections. In this study, we examined whether phentolamine can enhance the antibacterial activity of macrolide antibiotics against Gram-negative bacteria and investigated its mechanism of action. Methods: Synergistic effects between phentolamine and macrolide antibiotics were evaluated by checkerboard and time–kill assays and in vivo using a Galleria mellonella infection model. We utilized a combination of biochemical tests (outer membrane permeability, ATP synthesis, ΔpH gradient measurements, and EtBr accumulation assays) with scanning electron microscopy to clarify the mechanism of phentolamine enhancement of macrolide antibacterial activity against Escherichia coli. Results: In vitro tests of phentolamine combined with the macrolide antibiotics erythromycin, clarithromycin, and azithromycin indicated a synergistic action against E. coli test strains. The fractional concentration inhibitory indices (FICI) of 0.375 and 0.5 indicated a synergic effect that was consistent with kinetic time–kill assays. This synergy was also seen for Salmonella typhimurium, Klebsiella pneumoniae, and Actinobacter baumannii but not Pseudomonas aeruginosa. Similarly, a phentolamine/erythromycin combination displayed significant synergistic effects in vivo in the G. mellonella model. Phentolamine added singly to bacterial cells also resulted in direct outer membrane damage and was able to dissipate and uncouple membrane proton motive force from ATP synthesis that, resulted in enhanced cytoplasmic antibiotic accumulation via reduced efflux pump activity. Conclusions: Phentolamine potentiates macrolide antibiotic activity via reducing efflux pump activity and direct damage to the outer membrane leaflet of Gram-negative bacteria both in vitro and in vivo.

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“…Therefore, the treatment of CAG is particularly important. At present, the treatment of CAG in modern medicine mainly aims to improve the symptoms of patients by eradicating Hp infection, enhancing barrier function, and reducing bile reflux [ 17 , 18 , 19 ]. However, it has the disadvantage of a high recurrence rate.…”

Section: Classification Of Chronic Gastritismentioning

confidence: 99%

Treatment of Chronic Gastritis with Traditional Chinese Medicine: Pharmacological Activities and Mechanisms

Chen,

Wei,

et al. 2023

Pharmaceuticals

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Chronic gastritis (CG) is a common clinical digestive system disease, which is not easyily cured and is prone to recurrence. Traditional Chinese medicine (TCM) plays a significant role in the treatment of CG and has attracted increasing attention for clinical applications. In recent years, a large number of reports have shown that TCM has good therapeutic effect on CG. The aim of this paper is to investigate the pharmacological activities and mechanism of action of TCM in the treatment of CAG. Therefore, by searching the databases of Pubmed, China National Knowledge Infrastructure, Wanfang, and Baidu academic databases, this paper has summarized the molecular mechanisms of TCM in improving CG. The results show that the improvement of GC by TCM is closely related to a variety of molecular mechanisms, including the inhibition of Helicobacter pylori (Hp) infection, alleviation of oxidative stress, improvement of gastric function, repair of gastric mucosa, inhibition of inflammatory response, and apoptosis. More importantly, IRF8-IFN-γ, IL-4-STAT6, Hedgehog, pERK1/2, MAPK, PI3K-Akt, NF-κB, TNFR-c-Src-ERK1/2-c-Fos, Nrf2/HO-1, and HIF-1α/VEGF signaling pathways are considered as important molecular targets for TCM in the treatment of GC. These important findings will provide a direction and a basis for further exploring the pathogenesis of GC and tapping the potential of TCM in clinical treatment. This review also puts forward a bright prospect for future research of TCM in the treatment of CG.

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Efficacy of phentolamine combined with ambroxol aerosol inhalation in the treatment of pediatric severe pneumonia and its effect on serum IL-10 and CRP levels

Cited by 4 publications

References 26 publications

Phentolamine Protects against Apoptosis and Inflammation in a Neonatal Pneumonia Cell Model Induced by LPS by Regulating the TrkA/Akt Signaling Pathways

Phentolamine Protects against Apoptosis and Inflammation in a Neonatal Pneumonia Cell Model Induced by LPS by Regulating the TrkA/Akt Signaling Pathways

Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Treatment of Chronic Gastritis with Traditional Chinese Medicine: Pharmacological Activities and Mechanisms

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