title: OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS.
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.
authors.affiliation: Biophotonics Laboratory, Department of Electrical Engineering and Computer Science, University of Wisconsin Milwaukee 3200 N Cramer St., Milwaukee, WI 53211, USA.
authors.forename: Reyhaneh
authors.initials: R
authors.lastname: Sepehr
authors.affiliation: Department of Biomedical Engineering, Marquette University, 1515 W Wisconsin Avenue Milwaukee, WI 53233, USA.
authors.forename: Said H
authors.initials: SH
authors.lastname: Audi
authors.affiliation: Biophotonics Laboratory, Department of Electrical Engineering and Computer Science, University of Wisconsin Milwaukee 3200 N Cramer St., Milwaukee, WI 53211, USA.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Maleki
authors.affiliation: Biophotonics Laboratory, Department of Electrical Engineering and Computer Science, University of Wisconsin Milwaukee 3200 N Cramer St., Milwaukee, WI 53211, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Staniszewski
authors.affiliation: Department of Pediatrics, Cardiovascular Research Center Medical College of Wisconsin, 8701 Watertown Plank Rd Milwaukee, WI 53226, USA.
authors.forename: Annie L
authors.initials: AL
authors.lastname: Eis
authors.affiliation: Department of Pediatrics, Cardiovascular Center and Children's Research Institute, Medical College of Wisconsin CCC, Ste C410, 999 N92 St, Milwaukee, WI 53226, USA.
authors.forename: Girija G
authors.initials: GG
authors.lastname: Konduri
authors.affiliation: Biophotonics Laboratory, Department of Electrical Engineering and Computer Science, University of Wisconsin Milwaukee 3200 N Cramer St., Milwaukee, WI 53211, USA.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Ranji
keywords: FAD; Fluorescence imaging; Hyperoxia; LPS; NADH