Reactive species and pulmonary edema

Abstract

Pulmonary edema occurs when fluid flux into the lung interstitium exceeds its removal, resulting in hypoxemia and even death. Noncardiogenic pulmonary edema (NPE) generally results when microvascular and alveolar permeability to plasma proteins increase, one possible etiology being oxidant injury. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Experimental systems in which either RONS are increased or protective antioxidant mechanisms are decreased result in alterations of epithelial sodium channel activity and support the hypothesis that RONS are important in NPE. Both basic and clinical studies are needed to critically define the RONS–NPE connection and the capacity of antioxidant therapy (either alone or as a supplement to β-agonists) to improve patient outcome.

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury

“…The observation that nox4 −/− mice are fully protected against the perturbations to lung fluid balance that are characteristic of bleomycin-induced lung injury highlight Nox4 as a candidate interventional target for the management of disturbed fluid balance. ROS, NO, and H 2 O 2 are second messengers (33), and both ROS and NO regulate ENaC activity (33). Additionally, reports exist that indicate that oxidative stress, including exogenously applied H 2 O 2 , can both negatively (64) and positively (65,66) regulate ENaC expression and activity, demonstrating that the regulation of ENaC by oxidizing agents is complex, and that the source and compartmentalization of the oxidative agent likely influence the outcome of oxidative reactions on ENaC function.…”

“…ROS and NO can regulate alveolar fluid clearance (33) and ENaC activity (34,35). During a pathway screen, the cell-permeable nonspecific ROS quenchers polyethylene glycol (PEG)-complexed superoxide dismutase (Fig.…”

Oxidized glutathione (GSSG) inhibits epithelial sodium channel activity in primary alveolar epithelial cells

“…Nitric oxide, which can oxidize GSH leading to increased concentrations of GSSG, is increased in models of pulmonary edema (19,23,28,45). Studies also suggest that nitric oxide may impair glutathione reductase activity, effectively reducing the rate of GSSG conversion to GSH (5).…”

Prophylactic Administration of Curcumin Abates the Incidence of Hypobaric Hypoxia Induced Pulmonary Edema in Rats: A Molecular Approach

“…Noncardiogenic Pulmonary Edema (HAPE) generally results when micro vascular and alveolar permeability to plasma proteins increase, one possible etiology being oxidant injury [44]. Exposure to hypoxic conditions favors the increase of ROS from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase and nitric oxide synthase enzymes as well as establishing an inflammatory process leading to vasoconstriction and pulmonary edema [45,46].…”