Short-duration hyperoxia causes genotoxicity in mouse lungs: protection by volatile anesthetic isoflurane
| Autor: | Guru P. Maiti, Steven Idell, Kumuda C. Das, Venkatesh Kundumani-Sridharan, Somasundaram Raghavan, Trevor Walker, John D. Wasnick, Jaganathan Subramani, Cade Owens |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Male Physiology Supplemental oxygen Acute Lung Injury chemistry.chemical_element Hyperoxia medicine.disease_cause Oxygen Cell Line 03 medical and health sciences Mice 0302 clinical medicine Superoxides Physiology (medical) medicine Animals Short duration Lung Isoflurane business.industry Volatile anesthetic NADPH Oxidases Cell Biology respiratory system respiratory tract diseases 030104 developmental biology medicine.anatomical_structure chemistry Anesthesia medicine.symptom business 030217 neurology & neurosurgery Genotoxicity medicine.drug DNA Damage Research Article |
| Zdroj: | Am J Physiol Lung Cell Mol Physiol |
| ISSN: | 1522-1504 |
| Popis: | 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, isoflurane inhibits superoxide generation in hyperoxia. Additionally, isoflurane also protected the mouse lungs against ALI (95% O2for 36-h exposure). Our study established that short-duration hyperoxia causes genotoxicity in the lungs, which is abrogated when hyperoxia is used in conjunction with isoflurane, but isoflurane alone causes genotoxicity in the lung when delivered with ambient air. |
| Databáze: | OpenAIRE |
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