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

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 endot belial injury,contribute to impaired vascular growth and alveolar simplfcation soen in the lungs of premature infants with BPD.Hyperoxia induces ALI,reduces cell proliferation,cauuses DNA damage and promotes cell death by causi ng mitochondrial dys function.The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto fuorescent mitochondrial metabolic coenzymes,NADH and FAD in four different groups of rats.The ratio of these fluorescence signals(NA DH/FAD),referred to as NADH redox ratio(NADH RR)has been used as an indicator of tisue 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 mat lungs.We examined the tissue redox states of lungs from four groups of rat pups:nomoxic(21%O_(2))pups,hyperoxic(90%O_(2))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%docrease in lung tssue NADH RR as compared to that for normoxic lungs.LPS treatment alone or with hyperoxia had no significant ffect on lung tssue 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.