OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS.

Reyhaneh Sepehr,Said H Audi,Sepideh Maleki,Mahsa Ranji,Annie L Eis,Kevin Staniszewski,Girija G Konduri

doi:10.1142/s179354581350017x

Abstract

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

Highlights

Bronchopulmonary dysplasia (BPD) is a chronic lung condition that a®ects premature infants who receive supplemental oxygen or ventilator support for long periods of time
Despite the high morbidity and mortality rates of this illness, mechanisms underlying the development of Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) remain incompletely understood.8À11 Respiratory distress syndrome (RDS) in neonates occurs due to surfactant deciency and immaturity of the lung parenchyma and vasculature
The NADH redox ratio (NADH RR) is lower in the hyperoxia þ = À LPS groups compared to the normoxic þ = À LPS groups

Summary

Introduction

Bronchopulmonary dysplasia (BPD) is a chronic lung condition that a®ects premature infants who receive supplemental oxygen (hyperoxia) or ventilator support for long periods of time. Studies have shown that the premature lung can be acutely injured by either oxygen or mechanical ventilation, resulting in interference with or inhibition of lung alveolar and vascular development.1À3 Premature infants are more likely to be exposed to infection in utero or during postnatal life, which accelerates the subsequent development of BPD. Despite the high morbidity and mortality rates of this illness, mechanisms underlying the development of ARDS/ALI remain incompletely understood.8À11 Respiratory distress syndrome (RDS) in neonates occurs due to surfactant deciency and immaturity of the lung parenchyma and vasculature. One of the contributing factors in the development of ALI in premature babies is exposure to bacterial infection, including endotoxin from gram-negative bacteria.8À10,12À14 Exposure to supplemental oxygen, which is often used in the treatment of RDS, can contribute to lung injury

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