Short-duration hyperoxia causes genotoxicity in mouse lungs: protection by volatile anesthetic isoflurane

American Journal of Physiology. Lung Cellular and Molecular Physiology
Venkatesh Kundumani-SridharanKumuda C Das

Abstract

High concentrations of oxygen (hyperoxia) are routinely used during anesthesia, and supplemental oxygen is also administered in connection with several other clinical conditions. Although prolonged hyperoxia is known to cause acute lung injury (ALI), whether short-duration hyperoxia causes lung toxicity remains unknown. We exposed mice to room air (RA or 21% O2) or 60% oxygen alone or in combination with 2% isoflurane for 2 h and determined the expression of oxidative stress marker genes, DNA damage and DNA repair genes, and expression of cell cycle regulatory proteins using quantitative PCR and Western analyses. Furthermore, we determined cellular apoptosis using TUNEL assay and assessed the DNA damage product 8-hydroxy-2'-deoxyguanosine (8-Oxo-dG) in the urine of 60% hyperoxia-exposed mice. Our study demonstrates that short-duration hyperoxia causes mitochondrial and nuclear DNA damage and that isoflurane abrogates this DNA damage and decreases apoptosis when used in conjunction with hyperoxia. In contrast, isoflurane mixed with RA caused significant 8-Oxo-dG accumulations in the mitochondria and nucleus. We further show that whereas NADPH oxidase is a major source of superoxide anion generated by isoflurane in normoxia, isof...Continue Reading

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Citations

Aug 30, 2019·Current Opinion in Anaesthesiology·Lothar A SchwarteStephan A Loer
Mar 27, 2021·Frontiers in Medicine·Luciano AmarelleLeonel Malacrida
May 1, 2021·Toxicology Mechanisms and Methods·Rachel WatkinsBronwen Jugg
Sep 25, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Andreas M BeyerElizabeth R Jacobs

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Methods Mentioned

BETA
protein assay
ELISA
FACS
electron paramagnetic resonance
flow cytometry
X-ray
PCR

Software Mentioned

GraphPad Prism
FlowJo
Zeiss Zen
AxioVision
Xenon nano

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis