Resuscitation of hypoxic newborn piglets with oxygen induces a dose-dependent increase in markers of oxidation.
Newborn resuscitation with pure oxygen may be associated with long-term detrimental effects. Due to the change in attitude toward use of less oxygen upon resuscitation, there is a need to study effects of intermediate hyperoxia. The aim was to study dose-response correlation between inspiratory fraction of oxygen used for resuscitation and urinary markers of oxidative damage to DNA and amino acids. Hypoxemia was induced in newborn piglets following a standardized model; they were resuscitated for 15 min with either 21%, 40%, 60% or 100% oxygen and observed for 1 h. Urine samples were collected. Urinary elimination of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG), 2'deoxyguanosine (2dG), ortho-tyrosine (o-Tyr) and phenylalanine (Phe) were determined by HPLC and tandem mass spectrometry (HPLC-MS/MS). Quotient of 8-oxo-dG/2dG and o-Tyr/Phe ratios were significantly and dose-dependant higher in piglets resuscitated with supplementary oxygen. 8-oxodG/dG: Mean (SD) 5.76 (1.81) versus 22.44 (12.55) p < 0.01 and o-Tyr/Phe: 19.07 (10.7) versus 148.7 (59.8)for 21% versus 100%, p < 0.001. Hypoxia and subsequent resuscitation for 15 min with graded inspiratory fraction of oxygen causes increased oxidative stress and a dose-dependant oxidation of DNA and Phenylalanine. The increase in the hydroxyl attack may lead to a pro-oxidative status and risk for genetic instability.
Solberg
Rønnaug
R
Department of Pediatric Research, Medical Faculty, University of Oslo Rikshospitalet Medical Centre, Oslo, N-0027, Norway. ronnaug.solberg@medisin.uio.no
Andresen
Jannicke H
JH
Escrig
Raquel
R
Vento
Maximo
M
Saugstad
Ola Didrik
OD
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D000860:Hypoxia / Q000378:metabolism / Q000628:therapy*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010102:Oxygen Inhalation Therapy; D010649:Phenylalanine / Q000652:urine; D017382:Reactive Oxygen Species / Q000378:metabolism; D012121:Respiration, Artificial; D013552:Swine; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014443:Tyrosine / Q000652:urine
D015415:Biomarkers; D017382:Reactive Oxygen Species; D014443:Tyrosine; D010649:Phenylalanine; C026741:2-tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010100:Oxygen