Free Radicals in Inflammation

Cumpstey, Andrew F.; Feelisch, Martin

doi:10.1002/9783527692156.ch27

Cited by 11 publications

(8 citation statements)

References 107 publications

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“…ROS are essential for cellular signaling cascades and successful innate immune responses. However, ROS can also damage cellular structures through “oxidative stress,” resulting in inflammation and cell death ( 21 , 22 ). ROS concentrations in pulmonary endothelial cells increase exponentially with hyperoxia exposure, initiating a profound inflammatory response, endothelial cell injury, capillary leak and edema formation, culminating in cell death ( 23 ).…”

mentioning

confidence: 99%

Oxygen Targets During Mechanical Ventilation in the ICU: A Systematic Review and Meta-Analysis

Cumpstey

Oldman

Martin

et al. 2022

Critical Care Explorations

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OBJECTIVES: Patients admitted to intensive care often require treatment with invasive mechanical ventilation and high concentrations of oxygen. Mechanical ventilation can cause acute lung injury that may be exacerbated by oxygen therapy. Uncertainty remains about which oxygen therapy targets result in the best clinical outcomes for these patients. This review aims to determine whether higher or lower oxygenation targets are beneficial for mechanically ventilated adult patients. DATA SOURCES: Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, and Cochrane medical databases were searched from inception through to February 28, 2021. STUDY SELECTION: Randomized controlled trials comparing higher and lower oxygen targets in adult patients receiving invasive mechanical ventilation via an endotracheal tube or tracheostomy in an intensive care setting. DATA EXTRACTION: Study setting, participant type, participant numbers, and intervention targets were captured. Outcome measures included “mortality at longest follow-up” (primary), mechanical ventilator duration and free days, vasopressor-free days, patients on renal replacement therapy, renal replacement free days, cost benefit, and quality of life scores. Evidence certainty and risk of bias were evaluated using Grading of Recommendations Assessment, Development and Evaluation and the Cochrane Risk of Bias tool. A random-effects models was used. Post hoc subgroup analysis looked separately at studies comparing hypoxemia versus normoxemia and normoxemia versus hyperoxemia. DATA SYNTHESIS: Data from eight trials (4,415 participants) were analyzed. Comparing higher and lower oxygen targets, there was no difference in mortality (odds ratio, 0.95; 95% CI, 0.74–1.22), but heterogeneous and overlapping target ranges limit the validity and clinical relevance of this finding. Data from seven studies (n = 4,245) demonstrated targeting normoxemia compared with hyperoxemia may reduce mortality at longest follow-up (0.73 [0.57–0.95]) but this estimate had very low certainty. There was no difference in mortality between targeting relative hypoxemia or normoxemia (1.20 [0.83–1.73]). CONCLUSIONS: This systematic review and meta-analysis identified possible increased mortality with liberal oxygen targeting strategies and no difference in morbidity between high or low oxygen targets in mechanically ventilated adults. Findings were limited by substantial heterogeneity in study methodology and further research is urgently required to define optimal oxygen therapy targets.

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mentioning

confidence: 99%

Oxygen Targets During Mechanical Ventilation in the ICU: A Systematic Review and Meta-Analysis

Cumpstey

Oldman

Martin

et al. 2022

Critical Care Explorations

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“…Both electron and proton leaks occur physiologically and are responsible for the generation of ROS, specifically the leakage of incompletely reduced oxygen in the form of superoxide anions (O 2 •− ). 71 Superoxide then undergoes spontaneous and enzyme-catalysed dismutation to form hydrogen peroxide (H 2 O 2 ) and oxygen. 72 Although O 2 •− and H 2 O 2 are the two most abundant ROS and can exert their effects directly, their interactions with metals and other biomolecules can produce additional species with far greater reactivity, including the hydroxyl radical( • OH) and singlet oxygen ( 1 O 2 ), see Fig.…”

Section: Mechanisms Of Oxygen Toxicity—just Oxidative Stress?mentioning

confidence: 99%

Perioperative oxygenation—what's the stress?

Larvin,

Edwards,

Martin

et al. 2024

BJA Open

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“…Immune responses are the result of a complex interaction between immune cells and several soluble factors, aimed to protect the host from the invasion by microorganisms or to eliminate apoptotic cells at sites of tissue injury, thus maintaining tissue homeostasis [5]. However, an intense inflammatory response, not properly balanced by endogenous mechanisms of homeostatic control, can lead to cell and tissue damage with the production of free radicals [6]. To avoid excessive oxidative stress, cells use different mechanisms to activate the immune system including antioxidant defenses and purinergic signaling [4].…”

Section: Involvement Of Purinergic Signaling In Immune Responsesmentioning

confidence: 99%

“…This results in a sophisticated interaction between immune system cells and several molecules released by them to defend the organism against microorganisms or damaged cells from injured tissues and maintain tissue homeostasis [5]. Nevertheless, when the inflammatory responses are exacerbated and the mechanisms of homeostatic control do not work properly, this may trigger further tissue damage which is associated with several diseases [6]. Furthermore, purinergic signaling, comprised by an intricate network of receptors, enzymes, and signaling molecules, has been shown to participate in numerous cellular functions in the context of health and disease, especially immunomodulatory functions, since the components of the purinergic system are widely expressed in immune cells of several tissues [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between the Purinergic and Immune Systems: Implications for the Glutathione Antioxidant System in Health and Disease

Assmann¹,

Stefanello²,

Bottari³

et al. 2020

Glutathione System and Oxidative Stress in Health and Disease

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Glutathione (GSH) represents the major nonprotein thiol in cells and, alongside with glutathione-dependent enzymes such as glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST), exerts several biological functions including the protection against free radicals and other essential metabolic reactions within the body. Disturbances in the homeostasis of this complex glutathione antioxidant system may damage cells and have been implicated with the development and progression of several human diseases. In this context, the immune and purinergic systems are also essential, since the dysregulation in both systems may also be correlated with numerous diseases. These two networks are closely related and control inflammatory responses, especially by the crosstalk of signaling molecules, receptors, and enzymes; thus, they can exacerbate or slow down the progression of diseases. Based on this background, we aimed to provide a general scenario of the purinergic and immune systems and the connection between both and the modulation of glutathione and glutathione-dependent enzyme expression and activity in the context of health and disease.

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Free Radicals in Inflammation

Cited by 11 publications

References 107 publications

Oxygen Targets During Mechanical Ventilation in the ICU: A Systematic Review and Meta-Analysis

Oxygen Targets During Mechanical Ventilation in the ICU: A Systematic Review and Meta-Analysis

Perioperative oxygenation—what's the stress?

Crosstalk between the Purinergic and Immune Systems: Implications for the Glutathione Antioxidant System in Health and Disease

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