Effect of Different Dosages of Dexamethasone Therapy on Lung Function and Inflammation in an Early Phase of Acute Respiratory Distress Syndrome Model

Mikolka, Pavol; Kosutova, Petra; M, Kolomazník; Topercerova, Juliana; Kopincova, Jana; Čalkovská, Andrea; Mokrá, Daniela

doi:10.33549/physiolres.934364

Cited by 24 publications

(19 citation statements)

References 39 publications

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“…Dexamethasone is a synthetic corticosteroid that acts as an anti-inflammatory agent, widely affecting innate and acquired immune system via glucocorticoid receptor 118 , 119 . Low dose dexamethasone treatment significantly supresses neutrophil infiltration and subsequent pulmonary inflammation and significantly improves lung function in early phase of ARDS 120 . Lower respiratory tract transcriptomic profiling of patients with CoVID-19 associated ARDS shows dysregulated immunoregulation and inflammation.…”

Section: Is Butyrate An Alternative To Dexamethasone?mentioning

confidence: 93%

Is butyrate a natural alternative to dexamethasone in the management of CoVID-19?

et al. 2021

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Coronavirus disease 2019 (CoVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 has affected more than 100 million lives. Severe CoVID-19 infection may lead to acute respiratory distress syndrome and death of the patient, and is associated with hyperinflammation and cytokine storm. The broad spectrum immunosuppressant corticosteroid, dexamethasone, is being used to manage the cytokine storm and hyperinflammation in CoVID-19 patients. However, the extensive use of corticosteroids leads to serious adverse events and disruption of the gut-lung axis. Various micronutrients and probiotic supplementations are known to aid in the reduction of hyperinflammation and restoration of gut microbiota. The attenuation of the deleterious immune response and hyperinflammation could be mediated by short chain fatty acids produced by the gut microbiota. Butyric acid, the most extensively studied short chain fatty acid, is known for its anti-inflammatory properties. Additionally, butyric acid has been shown to ameliorate hyperinflammation and reduce oxidative stress in various pathologies, including respiratory viral infections. In this review, the potential anti-inflammatory effects of butyric acid that aid in cytokine storm depletion, and its usefulness in effective management of critical illness related to CoVID-19 have been discussed.

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Section: Is Butyrate An Alternative To Dexamethasone?mentioning

confidence: 93%

Is butyrate a natural alternative to dexamethasone in the management of CoVID-19?

et al. 2021

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“…In addition, the antimicrobial effect of erythromycin was enhanced by the combination of Sulfadimethoxine (at 200 mg/ml) and Trimethoprim (at 18 mg/ml), which blocks two steps in the biosynthesis of nucleic acids and proteins necessary for bacteria (synthesis of dihydrofolic acid and dihydrofolate reductase activity). In the drug, the included combination of antimicrobial components gives a broad spectrum of antibacterial action against Gram-positive and Gram-negative microorganisms, and dexamethasone (at 0.1 mg/ml) has an anti-inflammatory effect [ 17 , 18 ].…”

Section: Methodsmentioning

confidence: 99%

Parameters of nonspecific resistance of calves with respiratory pathology before and after treatment

et al. 2021

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Objective: The research was conducted to study the effect of a complex antimicrobial drug with an anti-inflammatory effect and an antimicrobial drug with an immunostimulating effect on the parameters of nonspecific resistance in calves. Materials and Methods: Two groups ( n = 5 each) of sick calves with respiratory pathology were selected for this study. For the treatment of the first experimental group, a complex antimicrobial drug Sulfetrisan ® was used. The second experimental group of the calves was intramuscularly injected with the experimental drug gentaaminoseleferon (GIA). To assess the cellular component of immunity in the blood before and after treatment, the number of white blood cells, T-lymphocytes, B-lymphocytes, phagocytic activity of leukocytes, phagocytic number, and phagocytic index (PhI) were determined. In addition, for assessing the humoral component, serum complement activity (SCA), serum lysozyme activity, serum bactericidal activity (SBA), circulating immune complexes (CIC), and total immunoglobulins (total Ig) were measured. The results were compared with the baseline parameters of healthy calves of the control group. Results: When studying the parameters of the humoral and cellular components of nonspecific resistance, it was found that in sick animals, compared with healthy ones, respiratory pathology was accompanied by an imbalance in the immune system. In the process of recovery in animals of the experimental groups under the effect of the drugs, positive changes occurred. However, many of the studied parameters did not reach the values of healthy animals. In the group of calves that received GIA, compared with the calves given Sulfetrisan ® , a significant increase in PhI ( p < 0.05), SBA ( p < 0.006), SCA ( p < 0.05), total Ig ( p < 0.0005), and CIC ( p < 0.05) was observed, which indicated an increase in natural resistance due to the immunostimulating action. Conclusion: The use of GIA in sick animals added to an increase in the general nonspecific cellular and humoral resistance of calves, which made it possible to increase therapeutic efficacy and shorten their recovery time.

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“…ARPE-19 cell viability decreased with PM 2.5 exposure in a dose-and time-dependent manner (Figure 1C), and was recovered by post-treatment with SFN for 6 h (Figure 1D and Supplementary Figure 1). DEX, a well-known anti-inflammatory drug (13,18), was used as a positive control. Furthermore, cellular LDH release significantly increased after 24 h exposure to PM 2.5 but decreased after treatment with 30 µM SFN (Figure 1E).…”

Section: Effects Of Sfn On Pm 25 -Induced Cell Death and Cytotoxicitymentioning

confidence: 99%

Sulforaphane Alleviates Particulate Matter-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells

et al. 2021

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Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and oxidative damage to retinal pigment epithelial (RPE) cells plays a major role in the pathogenesis of AMD. Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of <2.5 μm (PM2.5) causes respiratory injury, primarily due to oxidative stress. Recently, a large community-based cohort study in the UK reported a positive correlation between PM2.5 exposure and AMD. Sulforaphane (SFN), a natural isothiocyanate found in cruciferous vegetables, has known antioxidant effects. However, the protective effects of SNF in the eye, especially in the context of AMD, have not been evaluated. In the present study, we evaluated the effect of SFN against PM2.5-induced toxicity in human RPE cells (ARPE-19) and elucidated the molecular mechanism of action. Exposure to PM2.5 decreased cell viability in ARPE-19 cells in a time- and dose-dependent manner, potentially due to elevated intracellular reactive oxygen species (ROS). SFN treatment increased ARPE-19 cell viability and decreased PM2.5-induced oxidative stress in a dose-dependent manner. PM2.5-induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), a cell survival factor, was recovered by SFN. PM2.5 treatment decreased the enzymatic activities of the antioxidant enzymes including superoxide dismutase and catalase, which were restored by SFN treatment. Taken together, these findings suggest that SFN effectively alleviates PM2.5-induced oxidative damage in human ARPE-19 cells via its antioxidant effects, and that SFN can potentially be used as a therapeutic agent for AMD, particularly in cases related to PM2.5 exposure.

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Effect of Different Dosages of Dexamethasone Therapy on Lung Function and Inflammation in an Early Phase of Acute Respiratory Distress Syndrome Model

Cited by 24 publications

References 39 publications

Is butyrate a natural alternative to dexamethasone in the management of CoVID-19?

Is butyrate a natural alternative to dexamethasone in the management of CoVID-19?

Parameters of nonspecific resistance of calves with respiratory pathology before and after treatment

Sulforaphane Alleviates Particulate Matter-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells

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