Abstract
Recently, we demonstrated the utility of optical fluorometry to detect a change in the redox status of mitochondrial autofluorescent coenzymes nicotinamide adenine dinucleotide (NADH) and oxidized form of flavin adenine dinucleotide n}{}({rm FADH}_{2}) (FAD), as a measure of mitochondrial function in isolated perfused rat lungs (IPL). The objective of this paper was to utilize optical fluorometry to evaluate the effect of rat exposure to hyperoxia (n}{}{>}{95%}~{rm O}_{2} for 48 h) on lung tissue mitochondrial redox status of NADH and FAD in a nondestructive manner in IPL. Surface NADH and FAD signals were measured before and after lung perfusion with perfusate containing rotenone (ROT, complex I inhibitor), potassium cyanide (KCN, complex IV inhibitor), and/or pentachlorophenol (PCP, uncoupler). ROT- or KCN-induced increase in NADH signal is considered a measure of complex I activity, and KCN-induced decrease in FAD signal is considered a measure of complex II activity. The results show that hyperoxia decreased complex I and II activities by 63% and 55%, respectively, when compared to lungs of rats exposed to room air (normoxic rats). Mitochondrial complex I and II activities in lung homogenates were also lower (77% and 63%, respectively) for hyperoxic than for normoxic lungs. These results suggest that the mitochondrial matrix is more reduced in hyperoxic lungs than in normoxic lungs, and demonstrate the ability of optical fluorometry to detect a change in mitochondrial redox state of hyperoxic lungs prior to histological changes characteristic of hyperoxia.
Highlights
H IGH oxygen (O2) therapy is a necessary treatment of low blood O2 in adult and pediatric patients with acute lung injury (ALI) [1]–[3]
Mitochondrial complex I and II activities in lung homogenates were lower (77% and 63%, respectively) for hyperoxic than for normoxic lungs. These results suggest that the mitochondrial matrix is more reduced in hyperoxic lungs than in normoxic lungs, and demonstrate the ability of optical fluorometry to detect a change in mitochondrial redox state of hyperoxic lungs prior to histological changes characteristic of hyperoxia
This paper demonstrates the utility of optical fluorescent imaging for evaluating the effect of subacute rat exposure to hyperoxia on the redox state of lung tissue mitochondrial electron transport chain (ETC) in a non-destructive manner in isolated perfused lungs
Summary
H IGH oxygen (O2) therapy (hyperoxia) is a necessary treatment of low blood O2 in adult and pediatric patients with acute lung injury (ALI) [1]–[3]. This treatment is effective in restoring blood pO2 to a level which sustains vital organ metabolic requirements. Prolonged exposure to high O2 concentrations (>50%) causes lung injury [3]–[7]. Further complicating this situation is the fact that the time frame over which hyperoxic lung injury develops is difficult to predict due to the wide variation between patient tolerance/susceptibility [8]. Much work has been done in cell cultures and tissue homogenates, studies probing key tissue mitochondrial
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: IEEE journal of translational engineering in health and medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
