Open AccessImpact of inhaled oxygen on reactive oxygen species production and oxidative damage during spontaneous ventilation in a murine model of acute renal ischemia and reperfusion
Author(s) -
Melissa J. Kimlinger,
Eric H. Mace,
Raymond C. Harris,
Mingzhi Zhang,
Matthew B. Barajas,
Antonio Hernandez,
Frederic T. Billings
Publication year - 2021
Publication title -
medical research archives
Language(s) - English
Resource type - Journals
eISSN - 2375-1924
pISSN - 2375-1916
DOI - 10.18103/mra.v9i10.2575
Subject(s) - hyperoxia , reactive oxygen species , ischemia , kidney , medicine , oxidative stress , renal ischemia , hypoxia (environmental) , acute kidney injury , ventilation (architecture) , oxygenation , anesthesia , reperfusion injury , oxygen , pathology , lung , chemistry , biochemistry , mechanical engineering , organic chemistry , engineering
Acute kidney injury (AKI) affects 10% of patients following major surgery and is independently associated with extra-renal organ injury, development of chronic kidney disease, and death. Perioperative renal ischemia and reperfusion (IR) contributes to AKI by, in part, increasing production of reactive oxygen species (ROS) and leading to oxidative damage. Variations in inhaled oxygen may mediate some aspects of IR injury by affecting tissue oxygenation, ROS production, and oxidative damage. We tested the hypothesis that provision of air (normoxia) compared to 100% oxygen (hyperoxia) during murine renal IR affects renal ROS production and oxidative damage. Methods: We administered 100% oxygen or air to 8-9 week-old FVB/N mice and performed dorsal unilateral nephrectomy with contralateral renal ischemia/reperfusion surgery while mice spontaneously ventilated. We subjected mice to 30 minutes of ischemia and 30 minutes of reperfusion prior to sacrifice. We obtained an arterial blood gas (ABG) by performing sternotomy and left cardiac puncture. We stained the kidney with pimonidazole, a marker of tissue hypoxia; 4-HNE, a marker of ROS-production; and measured F 2 -isoprostanes in homogenized tissue to quantify oxidative damage. Results: Hyperoxia during IR increased arterial oxygen content compared to normoxia, but both groups of mice were hypoventilating at the time of ABG sampling. Renal tissue hypoxia following reperfusion was similar in both treatment groups. ROS production was similar in the cortex of mice (3.8% area in hyperoxia vs. 3.1% in normoxia, P=0.19) but increased in the medulla of hyperoxia-treated animals (6.3% area in hyperoxia vs. 4.5% in nomoxia, P=0.02). Renal F 2 -isoprostanes were similar in treatment groups (2.2 pg/mg kidney in hyperoxia vs. 2.1 pg/mg in normoxia, P=0.40). Conclusions: Hyperoxia during spontaneous ventilation in murine renal IR did not appear to affect renal hypoxia following reperfusion, but hyperoxia increased medullary ROS production compared to normoxia.