Hyperbaric oxygen preconditioning and the role of NADPH oxidase inhibition in postischemic acute kidney injury induced in spontaneously hypertensive rats

Autoři: Sanjin Kovacevic aff001;  Milan Ivanov aff002;  Zoran Miloradovic aff002;  Predrag Brkic aff003;  Una Jovana Vajic aff002;  Maja Zivotic aff004;  Nevena Mihailovic-Stanojevic aff002;  Djurdjica Jovovic aff002;  Danijela Karanovic aff002;  Rada Jeremic aff003;  Jelena Nesovic-Ostojic aff001
Působiště autorů: Department of Pathophysiology, Medical Faculty, University of Belgrade, Belgrade, Serbia aff001;  Institute for Medical Research, Department of Cardiovascular Physiology, University of Belgrade, Belgrade, Serbia aff002;  Department of Medical Physiology, Medical Faculty, University of Belgrade, Belgrade, Serbia aff003;  Department of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226974


Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI) and hypertension might contribute to the increased incidence of AKI. The purpose of this study was to investigate the effects of single and combined hyperbaric oxygen (HBO) preconditioning and NADPH oxidase inhibition on oxidative stress, kidney function and structure in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes, and 24h before AKI induction. For AKI induction, the right kidney was removed and ischemia was performed by clamping the left renal artery for 45 minutes. NADPH oxidase inhibition was induced by apocynin (40 mg/kg b.m., intravenously) 5 minutes before reperfusion. AKI significantly increased renal vascular resistance and reduced renal blood flow, which were significantly improved after apocynin treatment. Also, HBO preconditioning, with or without apocynin treatment showed improvement on renal hemodynamics. AKI significantly increased plasma creatinine, urea, phosphate levels and lipid peroxidation in plasma. Remarkable improvement, with decrease in creatinine, urea and phosphate levels was observed in all treated groups. HBO preconditioning, solitary or with apocynin treatment decreased lipid peroxidation in plasma caused by AKI induction. Also, combined with apocynin, it increased catalase activity and solitary, glutathione reductase enzyme activity in erythrocytes. While AKI induction significantly increased plasma KIM– 1 levels, HBO preconditioning, solitary or with apocynin decreased its levels. Considering renal morphology, significant morphological alterations present after AKI induction were significantly improved in all treated groups with reduced tubular dilatation, tubular necrosis in the cortico-medullary zone and PAS positive cast formation. Our results reveal that NADPH oxidase inhibition and hyperbaric oxygen preconditioning, with or without NADPH oxidase inhibition may have beneficial effects, but their protective role should be evaluated in further studies.

Klíčová slova:

Blood plasma – Hemodynamics – Hypertension – Kidneys – Lipid peroxidation – Oxidative stress – Oxygen – Renal ischemia


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