Effect of the NADPH oxidase inhibitor apocynin on septic lung injury in guinea pigs.

Wang, Weizheng; Suzuki, Yukio; Tanigaki, Toshimori; Rank, Douglas R.; Raffin, Thomas A.

doi:10.1164/ajrccm.150.5.7952574

Cited by 83 publications

(63 citation statements)

References 19 publications

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“…Use of apocynin blocks MAPK signal transduction and attenuates apoptotic cell death by blocking intrinsic and extrinsic signaling pathways during ischemia and reperfusion injury [30][31][32][33][34][35][36][37]. Several studies [21,38,39] have shown organ protective effects of apocynin by inhibition of cyclooxygenase metabolites in a variety of animal models. Cyclooxygenase byproducts such as thromboxane B2 play an important role to increase pulmonary vascular permeability and to induce pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 99%

Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

et al. 2011

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Rationale-Apocynin suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesized that apocynin attenuates VILI.Methods-VILI was induced by mechanical ventilation with tidal volume (V t ) of 15 ml/kg in isolated and perfused rat lung. Apocynin was administered in the perfusate at onset of mechanical ventilation. A group ventilated with low V t of 5 ml/kg served as control. Hemodynamics, lung Results-There was an increase in lung permeability and lung weight gain after mechanical ventilation with high V t , compared with low V t . Levels of inflammatory cytokines including interleukin-1b (IL-1b), tumor necrosis factor-alpha (TNF-a), and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; concentrations of carbonyl, thiobarbituric acid reactive substances, and H 2 O 2 were higher in perfusates and lung lavage fluids, and expression of myeloperoxidase, JNK, p38, and caspase-3 in lung tissue was greater in the high-Vt than in the low-Vt group. Administration of apocynin attenuated these inflammatory responses and lung permeability associated with decreased activation of nuclear factor-κB.Conclusions-VILI is associated with inflammatory responses including generation of ROS, cytokines, and activation of mitogen-activated protein kinase cascades. Administration of apocynin at onset of mechanical ventilation attenuates inflammatory responses and VILI in the isolated, perfused rat lung model.

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Section: Discussionmentioning

confidence: 99%

Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

et al. 2011

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“…Lipopolysaccharide (LPS), a constituent of the outer membrane of gram-negative bacteria, primes activation of the phagocytic NOX2 enzyme. In guinea pigs, LPS-stimulated ROS generation by neutrophils and ALI were significantly reduced with apocynin, a putative inhibitor of NOX2 (136,140). Emerging evidence suggests the presence of crosstalk between NOX enzymes and Toll-like receptors (TLRs), which cooperatively participate in the host innate immune response.…”

Section: Nox Enzymes In Acute Lung Injurymentioning

confidence: 99%

NOX Enzymes and Pulmonary Disease

Griffith

Pendyala²,

Hecker³

et al. 2009

Antioxidants & Redox Signaling

134

112

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The primary function of the lung is to facilitate the transfer of molecular oxygen (O 2 ; dioxygen) from the atmosphere to the systemic circulation. In addition to its essential role in aerobic metabolism, O 2 serves as the physiologic terminal acceptor of electron transfer catalyzed by the NADPH oxidase (NOX) family of oxidoreductases. The evolution of the lungs and circulatory systems in vertebrates was accompanied by increasing diversification of NOX family enzymes, suggesting adaptive roles for NOX-derived reactive oxygen species in normal physiology. However, this adaptation may paradoxically carry detrimental consequences in the setting of overwhelming=persistent environmental stressors, both infectious and noninfectious, and during the process of aging. Here, we review current understanding of NOX enzymes in normal lung physiology and their pathophysiologic roles in a number of pulmonary diseases, including lung infections, acute lung injury, pulmonary arterial hypertension, obstructive lung disorders, fibrotic lung disease, and lung cancer. Antioxid. Redox Signal. 11, 2505-2516.

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“…For example, the NAD(P)H oxidase inhibitor apocynin attenuated sepsis-induced lung injury, as well as neutrophil ROS generation in both guinea pigs and human umbilical vein endothelial cells [103], and polyethylene glycol-conjugated superoxide dismutase attenuated lung injury in E. coli-treated guinea pigs [104]. In a mouse model of ALI, administration of N-acetylcysteine 1 h after endotoxin challenge prevented the impairment of hypoxic pulmonary vasoconstriction and attenuated sepsis-associated ALI [105].…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Ventilator-associated lung injury: a search for better therapeutic targets

Oeckler¹,

Hubmayr²

2007

Eur Respir J

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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a continuum of injury that may arise from a number of primary insults.Localised injury may progress due to trauma from mechanical ventilation, a finding that has led to intense debate in the clinical and experimental literature over optimal ventilator management. The implementation of low tidal volume strategies has led to an improvement in outcomes; however, mortality remains unacceptably high.In the current review, ventilator-associated lung injury is examined, as it relates to the pathophysiological changes beyond direct airway trauma in ALI and ARDS, and an attempt is made to provide a historical perspective to outline potential current and future pitfalls in the use of surrogate end-points and the discovery of potential biomarkers. The systemic responses that lead to multi-organ dysfunction, the leading causes of morbidity and mortality in ALI and ARDS, are caused by pro-inflammatory signalling cascades and the activation of such diverse mediators as reactive oxygen species, immune response elements, apoptotic constituents and coagulation proteins.These areas are examined, including key mediators, and possible future areas of interest are discussed, including the potential of an ''acute lung injury chip'' to integrate measured surrogate biomarkers with real-time clinical information to improve patient outcomes.

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Effect of the NADPH oxidase inhibitor apocynin on septic lung injury in guinea pigs.

Cited by 83 publications

References 19 publications

Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

NOX Enzymes and Pulmonary Disease

Ventilator-associated lung injury: a search for better therapeutic targets

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