The Effects of Hyperoxia Exposure on Lung Function and Pulmonary Surfactant in a Rat Model of Acute Lung Injury

Abstract

2 The objective of this study was to determine if prolonged hyperoxia exposure would deplete antioxidants, resulting in excessive oxidative stress that would lead to oxidation of pulmonary surfactant and contribute to lung dysfunction. Rats were exposed to either hyperoxic (>95% O 2 ) or normoxic (21% O 2 ) oxygen concentrations for 48 or 60 hours. Pulmonary compliance, inflammatory cells, and total protein levels were measured as indicators of lung injury. Bronchoalveolar lavage (BAL) samples were analyzed for surfactant composition, antioxidant content, and markers of oxidative stress. Antioxidants were also measured in lung tissue and plasma samples. Hyperoxia exposure for 60 hours resulted in increased protein and inflammatory cells in BAL, and lower pulmonary compliance, compared to all other groups. Total surfactant and surfactant large aggregates were increased following 48 hours of hyperoxia exposure, with a further increase following 60 hours. Animals exposed to 60 hours of hyperoxia also demonstrated lower ascorbate levels in lung tissue, increased lipid peroxides in BAL, and increased oxidation of phosphatidylglycerol

Hydrogen-Rich Saline Provides Protection Against Hyperoxic Lung Injury

“…First, oxygen toxicity is believed to be mediated by the production and accumulation of excessive ROS, at levels exceeding the capacity of the lung antioxidant defense mechanisms [7]. Hydrogen could selectively react with exclusively detrimental ROS, such as hydroxyl radical and peroxynitrite, exerting protective effects, while not interaction with other physiological ROS, such as superoxide anion and H 2 O 2 , which possess physiologic roles [17].…”

“…It is generally accepted that increased generation of reactive oxygen species (ROS) plays an important role in lung injury during exposure to hyperoxia [7][8][9]. To evaluate antioxidant defenses, a principal focus of prior studies has been on antioxidant enzymes such as superoxide dismutase (SOD) [10,11], GSH peroxidase (GPx) [12,13], and peroxiredoxin 6 [14,15] utilizing both overexpression and suppression of activity.…”

Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved

“…HALI is a clinical syndrome characterized by extensive inflammation, accumulation of pleural fluid, disruption of the alveolar membrane, impaired gas exchange and respira-tory failure as a result of prolonged supplement of high concentrations of oxygen [2][3][4]. It is accepted that HALI is closely related to increased generation of reactive oxygen species (ROS), including superoxide (O 2 − ), hydrogen peroxide (H −2 O 2 ) and hydroxyl radical (·OH) [5,6]. Excessive ROS could react with DNA, lipids and proteins, leading to DNA breakage, lipid peroxidation and protein inactivation.…”

Lifespan and oxidative stress show a non-linear response to atmospheric oxygen inDrosophila

“…Rearing in pure oxygen (100% O 2 ) has been shown to increase the rate of ROS production (Beckman and Ames, 1998;Chance et al, 1979), levels of carbonylated (oxidized) proteins in houseflies (Sohal et al, 1993;Sohal and Dubey, 1994) and mitochondrial damage in Drosophila (Walker and Benzer, 2004). Moreover, pure oxygen is linked to the oxidative injury of mitochondrial enzymes such as cytochrome c oxidase (complex IV) (Walker and Benzer, 2004), aconitase and adenine nucleotide translocase (Das et al, 2001;Yan and Sohal, 1998), and induces brain damage (Kloek et al, 1978;Philpott et al, 1974), apotosis (Oh et al, 2008) and lung damage (Bin-Jaliah et al, 2009;Pace et al, 2009). Similarly, extreme hypoxia, and hypoxia followed by reoxygenation (reperfusion), can promote free radical production in vivo, as well as many types of oxidative injury Dirmeier et al, 2002;Duranteau et al, 1998;Yamamoto et al, 2006).…”